Membrane receptors for steroids and sterols

ABSTRACT

Four splice variants of a membrane receptor for steroids and sterols and their use are described.

[0001] The invention relates to nucleic acids that code for a membrane receptor for steroids and sterols, polypeptides and their use.

[0002] According to the standard model of steroid hormone action, the steroids bind to intracellular receptors that as ligand-activated transcription factors regulate the gene expression. It is common to refer to the direct action of the steroid hormones via their nuclear-position receptors to the transcription of target genes as genomic effects. Genomic effects are characterized by their time-delayed entry, i.e., more than 5 minutes up to several hours after hormone administration (McEwen et al. 1978 in: Reichlin et al. Eds., The Hypothalamus, Raven Press, p. 255 ff).

[0003] In contrast to the genomic actions, “quick” non-genomic effects that occur within a few seconds or minutes after the administration of steroid hormones and whose cause cannot lie in regulation of transcription have been observed for many years. Biochemical indicators for these effects are changes of membrane potential and/or the influencing of ion channels in the cell membrane (Watson et al. 1999, Proc Soc Exp Biol Med 220, 9 ff). These effects could be mediated by membrane-fixed receptors. Steroid effects that indicate the existence of a membrane receptor can also often be triggered by steroid derivatives that can no longer go through the plasma membrane by coupling to a bulky carrier molecule (for example serum albumin) and, made visible by fluorescence microscopy, bind to the cell surface. These results, just like binding studies with cell membranes and immune staining, indicate the existence of a membrane-fixed steroid receptor.

[0004] An example of a non-genomic action is the modulation of the γ-aminobutyric acid (GABA)-receptor by progesterone. This signal path is responsible for the mediation of the anesthetic action of progesterone (Covey, D. F. et al. 2000 J Pharmacol Exp Ther 293, 1009). Another example of a non-genomic progesterone action is the readmission of meiosis in amphibian oocytes. The progesterone-induced readmission of meiosis comprises the activation of cAMP-dependent protein kinases and the activation of MAPK signal paths (Palmer, A. et al. 2000 Prog Cell Cycle Res 4, 131 ff) and results in “germinal vesicle breakdown,” GVBD (Masui, Y. et al. 1971, J Exp Zool 177, 129 ff). While some findings suggest that the effects could be mediated via a membrane receptor for progesterone (mPR), the newest studies suggest that the nuclear-position PR could interact with tyrosine kinase signal paths (Tian, J. et al. 2000, Proc Natl Acad Sci USA 97, 14358 ff; Bayaa, M. et al. 2000, Proc Natl Acad Sci USA 97, 12607).

[0005] In a large number of publications, non-genomic estrogen effects are described for a great number of tissue and culture cells. Within a few minutes, the administration of estrogen triggers a number of effects: intracellular Ca²⁺ “spikes” (Mendoza, C.; Soler, A.; Tesarik, J. 1995, Biochem Biophys Res Commun 210: 518-523), stimulation of adenylate cylase (Aronica, S. M.; Kraus, W. L.; Katzenellenbogen, B. S., 1994, Proc Natl Acad Sci 91: 8517-21), and activation of NO-synthetase and phospholipase C (Le Mellay, V.; Grosse, B.; Lieberherr, M. 1997, J Biol Chem 272: 11902-11907).

[0006] Despite the extensive literature on non-genomic effects of steroid hormones, a membrane-fixed receptor for steroids in mammals previously could not be clearly identified. Should such a receptor exist, it would open up a quite new path for the development of medications. The provision of such a receptor is therefore the object of this invention.

[0007] The problem was solved by provision of a nucleic acid that comprises

[0008] a. The nucleotide sequence that is shown in Seq ID NO 1, NO 3, NO 5 and NO 7,

[0009] b. A nucleotide sequence that corresponds to the sequences of a. within the scope of the degeneration of the genetic code, or

[0010] c. A nucleotide sequence that hybridizes with the sequences of a. or b. under stringent conditions.

[0011] The term “hybridization under stringent conditions” according to this invention is defined in Sambrook et al. (Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory Press, 1989). A stringent hybridization exists, for example, when a hybridization signal is observed after washing for 1 hour with 1× SSC and 0.1% SDS at 50° C., preferably at 55° C., especially preferably at 62° C. and most preferably at 68° C., especially for 1 hour in 0.2× SSC and 0.1% SDS at 55° C., preferably at 62° C. and most preferably at 68° C. The nucleic acids, which hybridize under these conditions with the nucleic acid that is shown in Seq. ID NO 1 and/or 3 or a nucleotide sequence that corresponds to this sequence in the scope of the degeneration of the genetic code, are also the subject matter of this invention.

[0012] Nucleic acids can produce single- or double-stranded DNA, e.g., cDNA, or RNA, e.g., mRNA, cRNA, or pre-mRNA.

[0013] The nucleic acids that are shown in SEQ ID NOS 1, 3, 5 and 7 code for a membrane receptor for steroids and sterols. The four nucleic acids are splice variants of the same gene. The variants that are shown in SEQ ID NO 3 and SEQ ID NO 7 in each case have an insertion in the 5′ area of the sequence.

[0014] The sequences that are shown in Seq ID NOS 5 and 7 respectively contain a deletion between two ankyrin domains.

[0015] The nucleic acids that comprise a protein-coding section of the nucleic acid sequence that is shown in Seq ID NO 1, 3, 5 or 7 are preferred. A protein-coding section of the sequence that is shown in Seq ID NO 1 is in the nucleotide range of 227 to 6271, a coding range of the sequence that is shown in SEQ ID NO 3 is in the nucleotide range of 360 to 6482, the sequence that is shown in Seq ID NO 5 is in the nucleotide range of 227-6993, and the sequence that is shown in Seq ID NO 7 is in the nucleotide range of 360-6408.

[0016] The subject matter of the invention are also nucleic acids that code for a polypeptide with the amino acid sequence that is shown in Seq ID NO 2, 4, 6 or 8.

[0017] The nucleic acids according to the invention can be obtained from mammals, e.g., human cells, or from a cDNA library or a genomic library, which is obtained from, e.g., human cells. They can be isolated according to known techniques with use of short sections of the nucleic acid sequence that is shown in Seq ID NO 1, 3, 5 or 7 as hybridization probes or amplification primers.

[0018] In addition, the invention relates to polypeptides that are coded by a nucleic acid according to the invention. These polypeptides have the function of a steroid receptor.

[0019] In addition, the subject matter of the invention are polypeptides that comprise the amino acid sequence that is shown in Seq ID NO 2, 4, 6 or 8.

[0020] The polypeptides according to the invention can be recombinant polypeptides; natural, isolated polypeptides; or synthetic polypeptides.

[0021] The polypeptides according to the invention contain various domains: 12 so-called “leucine-rich repeats” (LRR), 3-ankyrin domains (ANK) and a kinase domain. These polypeptides are membrane-associated. After the binding of a steroid or sterol, the kinase domain phosphorylates serine and threonine radicals of proteins and thus initiates an intracellular signal cascade. The polypeptides according to the invention also contain a so-called “island” domain, which comprises 600 amino acids and is found between the 11th and 12th leucine-rich repeat domain of the polypeptide according to the invention. This domain is involved in the steroid or sterol bond.

[0022] The invention also relates to polypeptides that comprise the kinase domains of the polypeptides according to the invention or portions thereof. The kinase domain is found in, for example, the amino acid range of 1270 to 1565, whereby the numbering relates to the sequence that is shown in Seq ID No 2.

[0023] The subject matter of the invention are also polypeptides that comprise the island domain of the polypeptides according to the invention. The latter contains a steroid or sterol binding site.

[0024] The polypeptides of Seq ID NOS 2, 4, 6 and 8 according to the invention are preferably expressed in tissues, of which it is known that they are steroid hormone-sensitive. Examples are ovaries, fallopian tubes, prostates and blood.

[0025] The polypeptides according to the invention or partial areas thereof (peptides) can be used for the production of antibodies. For the production of polyclonal antibodies, the polypeptides or peptides can be bonded to, e.g., KLH (Keyhole Limpet Hemocyanin), and animals, e.g., rabbits, can be sprayed. They can also be used for the production of monoclonal antibodies. For antibody production, a polypeptide or peptide according to the invention or a mixture of several peptides according to the invention can be used. In this case, the production of antibodies is carried out according to standard processes as they are described in, e.g., Kohler, G. and Milstein, C., Nature 1975, 256, 495-497 and Nelson, P. N. et al., Mol. Pathol. 2000, 53, 111-117.

[0026] The subject matter of the invention are also the antibodies that are directed against a polypeptide according to the invention.

[0027] The antibodies according to the invention can be used for detecting the polypeptides according to the invention. This can be carried out by, e.g., immunohistochemistry. The antibodies according to the invention can also be used in other immune tests, such as, e.g., an ELISA (enzyme linked immunosorbent assay) or in radioimmuno tests. Thus, the concentration of polypeptide according to the invention can be detected in tissue or cell extracts.

[0028] The detection of the expression of the polypeptide according to the invention can also be carried out via the detection of mRNA in the cells. The subject matter of the invention is therefore also the use of a probe with nucleic acid sequences that are complementary to the nucleic acid sequences, which code for the peptides according to the invention, for the production of a reagent for detecting the presence of the mRNA according to the invention in cells. A probe is a short strand of DNA with at least 14 nucleotides. The probes according to the invention can be used in, e.g., a Northern Blot Analysis. This method is described in, e.g., Sambrook, J. et al., 1989, Cold Spring Harbor Laboratory Press. Other methods for detecting RNA are in situ hybridization, RNAse Protection Assay or PCR.

[0029] In addition, the subject matter of the invention are vectors that contain at least one copy of a nucleic acid according to the invention. Vectors can be prokaryotic or eukaryotic vectors. Examples of vectors are pPRO (Clontech), pBAD (Invitrogen), pSGS (Stratagene), pCl (Promega), pIRES (Clontech), pBAC (Clontech), PMET (Invitrogen), and pBlueBac (Invitrogen). The nucleic acids according to the invention can be introduced into these vectors with the methods that are known to one skilled in the art. The nucleic acids according to the invention are preferably found in connection with expression signals, such as, e.g, promoters and enhancers, in the vector.

[0030] The invention also relates to cells that are transfixed with a nucleic acid sequence according to the invention or with a vector according to the invention. As cells, e.g., E. coli, yeast, Pichia, Sf9, COS, CV-1 or BHK can be used. These cells can be used for the production of the polypeptides according to the invention or for test systems.

[0031] A subject of the invention is the use of the polypeptides according to the invention or the nucleic acids that code for them as a target substance for the production of an agent for treating sterol-dependent diseases or steroid hormone-dependent diseases.

[0032] The invention includes in particular the use of

[0033] a. A nucleic acid according to the invention,

[0034] b. A polypeptide according to the invention, or

[0035] c. A cell according to the invention for identifying effectors of a polypeptide according to the invention. Effectors are substances that have an inhibitory or activating effect on the polypeptide according to the invention and are able to influence the steroid receptor function of the polypeptides according to the invention.

[0036] In addition, the invention relates to a test system for identifying effectors of a polypeptide according to the invention, whereby a polypeptide according to the invention is incubated as a complete or partial sequence thereof with a steroid, a steroid analog or a sterol, and the amount of bound steroid, steroid analog or sterol is detected. As a partial sequence, e.g., the area that comprises the “leucine-rich repeats” and the island domain or shorter strands thereof can be used. The binding of the effectors can be measured, e.g., by labeled substances being used and the labeling (e.g., radioactivity or fluorescence) being measured. A displacement reaction can also be measured, however, by a binding labeled steroid being used and the displacement of the labeling by the receptor being measured after the addition of the substances to be tested.

[0037] This binding test can also be performed with a cell according to the invention that contains the polypeptide according to the invention. In addition to the binding of the substances that are to be tested, an intracellular effect can also be measured, such as, e.g., a change in Ca²⁺ concentration. This variant of the test system thus also provides an indication of a functional activity of the effector.

[0038] The subject matter of the invention is also a test system for identifying inhibitors of the kinase function of the polypeptide according to the invention, whereby a polypeptide according to the invention or its kinase domain is brought into contact with the substances to be tested, and the kinase activity is determined. In this case, the kinase activity is determined with and without the substance to be tested, and the extent of inhibition is determined.

[0039] The effectors of the sterol or steroid receptor function of the polypeptide according to the invention can be used for treating sterol-dependent diseases or steroid hormone-dependent diseases. Examples in this respect are perimenopausal and postmenopausal symptoms, diseases of the urogenital tract, ovarian dysfunction, osteoporosis, benign prostate hyperplasia, cardiovascular diseases, vascular diseases, neurodegenerative diseases, inflammatory diseases, and diseases of the immune system. In addition, these effectors can be used for treatment of female and male infertility.

[0040] It has been found that the polypeptide according to the invention binds the endogenous substance FF-MAS (meiosis-activating substance that consists of follicular liquid). FF-MAS induces the meiosis of female germ cells and is therefore an essential factor of female fertility. With the aid of a test system according to the invention, substances can be identified that inhibit the effect of FF-MAS on the receptor. These substances inhibit the fertility and can therefore be used as agents for birth control. Substances that activate the receptor and therefore act analogously to FF-MAS can also be identified with the test system according to the invention. These substances act to promote fertility and can either be administered to women who suffer from fertility disorders or they can be added in vitro to an oocyte culture. The thus prepared oocytes are then used for in vitro fertilization.

[0041] In addition, the invention relates to a process for the preparation of a pharmaceutical agent, whereby

[0042] a. Substances are brought into contact with a test system according to the invention,

[0043] b. The action of the substances on the test system is measured in comparison to controls,

[0044] c. A substance that shows a modulation of the activity of the polypeptides according to the invention in step b. is identified,

[0045] d. And the substance that is identified in step c. is mixed with the formulation substances that are commonly used in pharmaceutics.

[0046] Activity of the polypeptide according to the invention is defined as the steroid-binding property and/or the kinase activity of the polypeptide.

[0047] A substance that is identified by a process according to the invention can optionally be optimized relative to metabolic stability, activity in a test system according to the invention and/or bio-availability. Methods that are standard in chemistry can be used in this respect.

DESCRIPTION OF THE FIGURES

[0048]FIG. 1 shows the domain structure of the polypeptides according to the invention. The structure begins to the left with the N-terminus.

[0049]FIG. 2 shows the result of an electronic Northern Blot Analysis.

[0050]FIG. 3 shows a sequence comparison of the DNA of all 4 splice variants. Here, the designation

[0051] SINGER_KINASE_SP1B corresponds to Seq ID No 5,

[0052] SINGERKINASE_SP2B corresponds to Seq ID No 7,

[0053] spliceVariant_(—)2a corresponds to Seq ID No 3 and

[0054] singerKinase_sp1a corresponds to Seq ID No 1.

[0055]FIG. 4 shows a comparison of the amino acid sequences of all 4 splice variants. The designations are explained under FIG. 3.

[0056]FIG. 5 shows the distribution of the RNA according to the invention in various human tissues. For the amplification, the following primers were used: 5′ gtatgaactgtgctgtgggaag 3′ (4928) and 5′ gatgtaccactccaccacctacc 3′ (5532). A Northern Blot is shown.

[0057] In the left picture, 1 refers to the spleen, 2 refers to the thymus, 3 refers to the prostate, 4 refers to the testis, 5 refers to the ovary, 6 refers to the small intestine, 7 refers to the colon, and 8 refers to peripheral blood leukocytes. In the right picture, 1 refers to the brain, 2 refers to the heart, 3 refers to the skeletal muscles, 4 refers to the colon, 5 refers to the thymus, 6 refers to the spleen, 7 refers to the kidney, 8 refers to the liver, 9 refers to the small intestine, 10 refers to the placenta, 11 refers to the lung, and 12 refers to peripheral blood leukocytes. The arrow shows the position of the strip that corresponds to the RNA according to the invention.

[0058]FIG. 6 shows the expression and auto-phosphorylation of the kinase domains. In FIG. 1, a polyacrylamide gel is shown after protein staining with Coomassie G-250; in FIG. 2, the corresponding autoradiogram (³³P) in shown, and in FIG. 3, a Western Blot is shown. Here: a refers to glutathione eluate (control), b refers to glutathione eluate (GST-SIN2), c refers to glutathione sepharose with bonded proteins (control), d refers to glutathione sepharose with bonded proteins (GST-SIN2), e+f mean molecular weight markers (SeaBlue), g refers to the SDS-eluate of the glutathione sepharose (control), and h refers to the SDS-eluate of the glutathione sepharose (GST-SIN2). The test conditions are described in Examples 3 and 4. The Western Blot was produced with anti-GST-antibodies (goat serum) as a first antibody and anti-goat IgG-alkaline phosphatase conjugate as a second antibody. The arrow marks the position of the GST-kinase fusion protein.

[0059]FIG. 7 shows the amino acid sequence of the fusion protein that consists of glutathione-S-transferase and the amino acids Ala1267-Leu1570.

EXAMPLES

[0060] The molecular biological methods that are used in the examples, such as, e.g., polymerase chain reaction (PCR), production of cDNA, cloning of DNA, sequencing of DNA, were performed as described in known textbooks, such as in, for example, Molecular Cloning, A Laboratory Manual (Sambrook, J. et al., 1989, Cold Spring Harbor Laboratory Press).

Example 1 Cloning of the Membrane-Bound Steroid Receptor

[0061] For the cloning, a cDNA bank from the human mammary gland (Clontech) was used. The cDNA of the splice variants according to the invention was obtained by means of PCR. To this end, the following primers were used: N-ter- 5′-ATGGAGACGCTTAACGGTGC-3′ minal area #3F 5′-GTTCCCTGTCATCGTGCGCTTGCCCC-3′ (790-815) #4F 5′-CCAGCAACAAGTTGTCCCACCTCCC-3′ (1233-1257) #5F 5′-GGATCTCTCCAGAAACCAACTTGGC-3′ (1729-1753) #6F 5′-CCTGGAGATCTTACAGACGGGGAGGG-3′ (2269-2294) #7F 5′-CGTCGGCAGCACCATCGGCTGCCAG-3′ (2824-2848) #8F 5′-CCTCCTGCCCCATCTCCTTCCATC-3′ (3307-3330) #9F 5′-GAAATCAGAGGATGTGCAGTACTTC-3′ (3880-3904) #10F 5′-CACCGTGCTGTCCGAGAACGCCAG-3′ (4369-4392) #11F 5′-CCTTCATGTATGAACTGTGCTGTG-3′ (4920-4943) #12F 5′-CCATGGTTACGTCAGTCGTGTGC-3′ (5424-5446) #13F 5′-CCGACAGGTCTGAGCATGACCTG-3′ (5886-5908) #2R 5′-TTACCTTCTCTTGCGAGTGCAAGCC-3′ (6247-6271) C-ter- 5′`GAGAACTCTGCTCCAGAGAAC 3′. minal

[0062] For the amplification of the splice variants, which are shown in Seq Id Nos 1 and 3, the primer 5′-CGGATGACAACCCAGCCGTGGTGG-3′ (579-602) was also used. The numbering indicated in parentheses relates to the sequence that is shown in Seq ID No 1.

Example 2 Expression of the Membrane-Bound Steroid Receptor

[0063] For the expression, the coding area was amplified by means of PCR and introduced into the baculovirus expression vector pBlueBac4.5/V5-His-TOPO (Invitrogen) or the eukaryotic expression vector pcDNA3.1/V5/His-TOPO (Invitrogen). To simplify detection and purification, a fusion with an His tag was carried out. After co-transfection of insect cells with the Bac-N-Blue DNA, recombinant viruses were produced that were identified by a PCR process. A phage stock was then applied and used in larger amounts for further transfections and production of the receptor. The purification of the His-tagged proteins was carried out on a nickel affinity column.

Example 3 Cloning and Expression of the Kinase Domain

[0064] The kinase domain was amplified within a sizeable sequence from a cDNA library (mammary gland and lung, Clontech) by PCR and cloned in the TOPO vector. From this vector, only the kinase domain is amplified out.

[0065] For expression of the recombinant kinase domain as a glutathione-S-transferase-fusion protein, the vector pGex-KT (contains thrombin interfaces between the proteins) is used, and for fusion with MBP, the vector pMal-TBVp3 (modified, also with thrombin interfaces) is used. Within the context of cloning, the plasmids are transformed for the time being into the E. coli strain XL-1 and then for the expression of proteins into the E. coli strain BL21. The transformation is always carried out by thermal shock. The cells are cultivated in LB medium with 200 μg/ml, whereby in the expression of MBP-fusion proteins, 0.1% glucose must always be present in the medium.

[0066] In the expression of proteins, the cells grow up to an OD₆₀₀ of 0.8-0.9, then the induction is carried out with 0.5 mmol of IPTG for 3 hours at 25° C. Cell decomposition takes place in the French Press. The decomposition buffer contains 20 mmol of Tris, pH 7.4, 150 mmol of NaCl, 1 mmol of DTT, 0.1 mmol of EDTA and protease inhibitor. To separate the insoluble components, an ultracentrifuging is carried out at 35000×g after the cell decomposition. The MBP-fusion proteins are then purified on amylose resin in the buffer (20 mmol of Tris, pH 7.4, 150 mmol of NaCl, 1 mmol of DTT, 0.1 mmol of EDTA and protease inhibitor). The GST-fusion proteins are purified on sepharose beads (buffer as above).

[0067] In another approach for the expression of the recombinant kinase domain as a glutathione-S-transferase-fusion protein, the eukaryotic expression vector pDEST27 (Invitrogen 11812-013) is used.

[0068] This vector carries the cDNA that codes the kinase domain according to the invention in the reader frame of the N-terminal upstream glutathione-S-transferase CDNA. This results in the expression of a fusion protein from glutathione-S-transferase and the amino acids Ala1267-Leu1570 (amino acid numbering according to Seq ID No 2).

[0069] For the expression of the recombinant kinase domain, HEK293EBNA cells (Invitrogen) are transiently transfixed with the kinase-domain-coding pDEST27 vector. To this end, HEK293EBNA cells are cultivated in the DMEM medium (plus 10% FCS, plus Glutamax) until subconfluence is completed. The cells in a flask are transfixed according to the standard protocol of the manufacturer by means of lipfectamine reagent (Invitrogen). 150 μl of reagent and 75 μg of pDEST27-kinase domain DNA are used for transfection per 150 cm² flask (=GST-SIN2). The cells of a second flask are not transfixed (=control).

[0070] The cells are harvested after 48 hours of incubation: the conditioned medium is discarded. The cells are lysed on ice (25 mmol of HEPES/NaOH, pH 7.3+1% NP-40+2 mmol of EGTA+2 mmol of EDTA+10 mmol of β-glycerophosphate+2 mmol of DTT+phosphatase inhibitor cocktail No. 1 (SIGMA)+phosphatase inhibitor cocktail No. 2 (SIGMA)+Complete_(mini)-EDTA (Roche)+200 mmol of NaCl), frozen, thawed and centrifuged. The cell supernatant is further used.

[0071] For binding the GST-fusion protein to glutathione sepharose, the cell supernatant is added to the glutathione sepharose, incubated and washed. 20 μl of the glutathione sepharose with the proteins bonded thereto is used directly in the kinase assay as described in Example 4 (=glutathione sepharose with bonded proteins). The residual glutathione sepharose is eluted with a buffer that contains reduced glutathione (=glutathione eluate).

Example 4 Detection of the Activity of the Kinase Domain (Auto-phosphorylation)

[0072] 10 μl each of the purified protein solution (see Example 3, glutathione sepharose with bonded proteins and glutathione eluate) is mixed with 10 μl of kinase assay buffer (25 mmol of HEPES/NaOH, pH 7.3+10 mmol of MgCl₂+10 mmol of MnCl₂+2 mmol of DTT+phosphatase inhibitor cocktail Nos. 1 and 2 (SIGMA)+200 mmol of NaCl). The phosphorylation reaction is started by adding 1 μl each of 100 μM ATP+4 μCi γ[³³P]-ATP1. The reaction is carried out for 60 minutes at 30° C. The samples are separated in an SDS-PAGE, and the gel is stained with a Coomassie G-250 solution. After the gel is dried, an autoradiography is carried out.

Example 5 Test System for Finding Effectors (Binding Assay) Homogenization

[0073] Cells and tissue, in which the protein according to the invention is expressed, were homogenized in buffer 1 at 4° C. Buffer 1:0.02 mmol/l of tris-buffer, pH 7.5, 0.5 mmol/l of EDTA, 2 mmol/l of DTT, 20% glycerol, 0.4 M KCL, 20 mmol/l of molybdate, 0.3 μmol/l of aprotinin, 1 μmol/l of pepstatin, 10 μmol/l of leupeptin.

Receptor Binding Studies

[0074] Receptor binding studies were performed with crude extracts in buffer 1, cytosol preparations (supernatant after centrifuging the crude extract at 105,000×g, 90 minutes) and microsome fractions of cells and tissues that express the protein according to the invention.

[0075] Crude extracts and cytosol fractions (0.04 ml) were incubated at 4° C. for 2 hours with 10 μl of radioactive steroid or sterol (concentration in the batch 10 nmol/l) either in the absence or in the presence of a 100× excess of a non-radioactive substance (for determining the unspecific bond). After the incubation of the crude extract or the cytosol fraction with the radioactive steroids or sterols, unbound steroids or sterols were adsorbed in activated carbon by being incubated with 0.25 ml of a suspension of dextran-coated charcoal in buffer 1 for 5 minutes at 4° C. After centrifuging (5 minutes, 15,000 g), an aliquot of the supernatant was removed, and the radioactivity was determined by means of a scintillation counter. The specific receptor bond was determined as the difference between the bound radioactivity in the absence and in the presence of a 100× excess of a non-radioactive compound. As radiolabeled steroids and sterols, ³[H]-estradiol, ³[H]-progesterone, ³[H]-corticosterone, ³[H]-cortisol, ³[H]-aldosterone, ³[H]-dihydrotestosterone, ³[H]-testosterone, ³[H]-pregnenolone, ³[H]-cholesterol, ³[H]-androsterone, ³[H]-dihydroandrosterone, ³[H]-calcitriol and ³[H]-FF-MAS were used.

Example 6 Kinase Assay

[0076] The peptide that contains the kinase domains is expressed in SF9 or COS cells and purified via affinity chromatography (tag). The purified peptide is incubated in 20 mmol of Mops, pH 7.5, 25 mmol of β-glycerophosphate; 5 mmol of EGTA; 0.04% NP40 and 0.2% BSA in the kinase assay for 30 minutes with ³³P-ATP in MgCl₂ and the substrate Bio-Lys-Lys-Leu-Asn-Arg-Thr-Leu-Ser-Val-Ala-OH. This substrate is phosphorylated in the presence of ATP on serine or threonine and can be detected with the aid of streptavidin beads. The reaction is completed with 50 μm of ATP, 50 μm of EDTA, 0.1% Triton X-100 (v/v) and simultaneously mixed with the streptavidin beads. The reaction batches must be left for at least 10 minutes and then centrifuged for 10 minutes. The determination of the phosphorylation is carried out by measuring the radioactivity. Staurosporine is used as a reference substance for inhibiting the kinase activity of peptides.

Example 7 Electronic Northern

[0077] Based on the number of ESTs for a certain tissue, an electronic Northern provides an indication to the expression strength of a certain gene in this tissue. First, the number of all ESTs for a tissue is identified in a data bank (named pool-size), and then the number of ESTs of this tissue, which correspond to the nucleic acid according to Seq ID No. 1, is determined (named hits). As a method, a so-called “blast search” is used (NCBI BLAST v. 2.0.10; Altschul et al., Nucleic Acid Res. 1997, 25, 3389-3402). A search is run in an EST-data bank (LifeSeqGold from Incyte).

1 26 1 7093 DNA Homo sapiens 1 cgaggggacg cctcgcgacg gttcctggga gagctggcgg cggccttgct ctgcgcgctc 60 ttcgcgccgc cctccccgcc cgcccgcctc aggattgagg aagtgcgtct gggcccggcc 120 ccggcgcggg gggcagacgg cggtgggacg gccaggcccc ggccccgcca gtgtgtccgc 180 ccggccccgc gtcccggagg agtcagctgt gtgtccagaa cgtgccatgg agacgcttaa 240 cggtgccggg gacacgggcg gcaagccgtc cacgcggggc ggtgaccctg cagcgcggtc 300 ccgcaggacg gaaggcatcc gcgccgcgta caggcgggga gaccgcggcg gcgcccggga 360 cctgctggag gaggcctgcg accagtgcgc gtcccagctg gaaaagggcc agcttctgag 420 catcccggca gcctatgggg atctggagat ggtccgctac ctactcagca agagactggt 480 ggagctgccc accgagccca cggatgacaa cccagccgtg gtggcagcgt attttggaca 540 cacggcagtt gtgcaaaata cgctgcccac cgagcccacg gatgacaacc cagccgtggt 600 ggcagcgtat tttggacaca cggcagttgt gcaggaattg cttgagtcct taccaggtcc 660 ctgcagtccc cagcggcttc tgaactggat gctggccttg gcttgccagc gagggcacct 720 gggggttgtg aagctcctgg tcctgacgca cggggctgac ccggagagct acgctgtcag 780 gaagaatgag ttccctgtca tcgtgcgctt gcccctgtat gcggccatca agtcagggaa 840 tgaagacatt gcaatattcc tgcttcggca tggggcctat ttctgttcct acatcttgct 900 ggatagtcct gaccccagca aacatctgct gagaaagtac ttcattgaag ccagtccctt 960 gcccagcagt tatccgggaa aaacagctct ccgtgtgaaa tggtcccatc tcagactgcc 1020 ctgggtagac ctagactggc tcatagacat ctcctgccag atcacggagc tcgacctttc 1080 tgccaactgc ctggcgaccc tcccctcggt tatcccctgg ggcctcatca atctccggaa 1140 gctgaacctc tccgacaacc acctggggga gctgcctggc gtgcagtcat cggacgaaat 1200 catctgttcc aggctacttg aaattgacat ttccagcaac aagttgtccc acctccctcc 1260 tggattcttg cacctctcaa aacttcaaaa actgacagct tcaaaaaatt gtttagaaaa 1320 attgttcgaa gaagaaaatg ccactaactg gataggttta cggaagctac aggaacttga 1380 tatatctgac aataaattga cagaactccc tgccctgttc cttcactctt tcaagtccct 1440 caattctctg aatgtctcca gaaacaacct gaaggtgttt ccagatccct gggcctgccc 1500 tttgaaatgt tgtaaagctt ccagaaatgc cctggaatgt ctgccagaca aaatggctgt 1560 cttttggaaa aatcacctga aggatgtgga tttctcagaa aacgcactca aagaagttcc 1620 cctgggactt ttccagcttg atgccctcat gttcttgagg ttacagggga accagctggc 1680 ggcacttcca cctcaagaga agtggacctg caggcagctc aaaaccctgg atctctccag 1740 aaaccaactt ggcaaaaatg aagatggact gaaaacgaag cgtattgcct ttttcaccac 1800 cagaggtcgc cagcgctccg ggactgaggc agagacaact atggagttca gtgcatctct 1860 ggtaaccatt gtgttcctgt ctaacaactg taacctctgt gcatacacat gtgcagcaag 1920 tgtgctggaa tttccggcct tcctaagtga gtctttggaa gtcctttgcc tgaacgacaa 1980 ccacctcgac acagtccctc cctcggtttg cctactgaag agcttatcag agctctactt 2040 gggaaacaac cctggcctcc gggagctccc tcctgagctg gggcagctgg gcaacctctg 2100 gcagctggac actgaagacc tgaccatcag caatgtgcct gcagaaatcc aaaaagaagg 2160 ccccaaagca atgctgtctt acctgcgtgc tcagctgcgg aaagcggaaa agtgcaagct 2220 gatgaagatg atcatcgtgg gtcccccgcg ccagggcaag tccaccctcc tggagatctt 2280 acagacgggg agggcccccc aggtggtgca tggagaggcc accatcagga ccaccaagtg 2340 ggagctccag aggccggctg gctcgagagc caaggtcaag gatggtctgc gtgcagagtc 2400 cctgtgggtt gagtccgtgg agttcaacgt ctgggacatc gggggaccgg ccagcatggc 2460 cactgtcaac cagtgcttct tcacggacaa ggccctgtac gtggtggtct ggaacctggc 2520 gctgggggag gaggccgtgg ccaacctcca gttctggctg ctcaacatcg aggccaaggc 2580 cccaaacgcc gtggtgctgg tggtcgggac gcacctggat ttaattgaag ccaagttccg 2640 tgtggaaagg attgcaacgc tgcgtgccta tgtgctggca ctctgccgct ccccctccgg 2700 ctccagggcc acaggcttcc cagacatcac cttcaaacac ttacatgaga tttcctgcaa 2760 gagcctggaa ggtcaggaag ggctgcgaca gctgattttc cacgtcacgt gcagcatgaa 2820 ggacgtcggc agcaccatcg gctgccagcg actggcaggg cggctgatcc ccaggagcta 2880 cctgagcctg caggaggccg tgctggcaga gcagcagcgc cgcagccggg acgacgacgt 2940 gcagtacctg acggacaggc agctggagca gctggtggag cagacgcccg acaacgacat 3000 caaggactac gaggacctgc agtcagccat cagcttcctc atagaaaccg gcaccctgct 3060 ccatttcccg gacaccagcc acggcctgag gaacctctac ttcctcgacc ctatttggct 3120 ctccgaatgt ctgcagagga tctttaatat taagggctct cggtcagtgg ccaagaatgg 3180 ggtgatcaga gcagaagacc tcaggatgct gctggtgggg actggcttca cgcagcagac 3240 ggaagagcag tacttccagt tcctggccaa gtttgagatc gccctgcccg tcgccaatga 3300 cagctacctc ctgccccatc tccttccatc taaacctggc ctggacaccc acggtatgcg 3360 gcaccccaca gccaacacca ttcagagggt atttaagatg agcttcgttc ccgttggctt 3420 ctggcaaagg tttatagcac ggatgctgat cagcctggcg gagatggacc tgcagctttt 3480 tgaaaacaag aagaatacta aaagcaggaa caggaaagtc accatttaca gttttacagg 3540 aaaccagaga aatcgctgta gcacattcag agtgaaaaga aatcagacca tctattggca 3600 ggaagggctc ctggtcactt ttgatggggg ctacctcagt gtggaatctt ccgacgtgaa 3660 ctggaaaaag aagaaaagcg gaggaatgaa aattgtttgc caatcagaag tgagggactt 3720 ctcagccatg gctttcatca cggaccacgt caattccttg attgatcagt ggtttcccgc 3780 cctgacagcc acagagagcg acgggacgcc actcatggag cagtacgtgc cctgcccggt 3840 ctgcgagaca gcctgggccc agcacacgga ccccagtgag aaatcagagg atgtgcagta 3900 cttcgacatg gaagactgtg tcctgacggc catcgagcgg gacttcatct cctgccccag 3960 acacccggac ctccccgtgc cgctgcagga gctggtccct gaactgttca tgaccgactt 4020 cccggccagg ctcttcctgg agaacagcaa gctggagcac agcgaggacg agggcagcgt 4080 cctgggccag ggcggcagtg gcaccgtcat ctaccgggcc cggtaccagg gccagcctgt 4140 ggccgtcaag cgcttccaca tcaaaaaatt caagaacttt gctaacgtac cggcagacac 4200 catgctgagg cacctgcggg ccaccgatgc catgaagaac ttctccgagt tccggcagga 4260 ggccagcatg ctgcacgcgc tgcagcaccc ctgcatcgtg gcgctcatcg gcatcagcat 4320 ccacccgctc tgcttcgccc tggagctcgc gccgctcagc agcctcaaca ccgtgctgtc 4380 cgagaacgcc agagattctt cctttatacc cctgggacac atgctcaccc aaaaaatagc 4440 ctaccagatc gcctcgggcc tggcctacct gcacaagaaa aacatcatct tctgtgacct 4500 gaagtcggac aacattctgg tgtggtccct tgacgtcaag gagcacatca acatcaagct 4560 atctgactac gggatttcga ggcagtcatt ccatgagggc gccctaggcg tggagggcac 4620 tcctggctac caggccccag agatcaggcc tcgcattgta tatgatgaga aggtagatat 4680 gttctcctat ggaatggtgc tctacgagtt gctgtcagga cagcgccctg cactgggcca 4740 ccaccagctc cagattgcca agaagctgtc caagggcatc cgcccggttc tggggcagcc 4800 ggaggaagtg cagttccggc gactgcaggc gctcatgatg gagtgctggg acactaagcc 4860 agagaagcga ccgctggccc tgtcggtggt gagccagatg aaggacccga cttttgccac 4920 cttcatgtat gaactgtgct gtgggaagca gacagccttc ttctcatccc agggccagga 4980 gtacaccgtg gtgttttggg atggaaaaga ggagtccagg aactacacgg tggtgaacac 5040 agagaagggc ctcatggagg tgcagaggat gtgctgccct gggatgaagg tgagctgcca 5100 gctccaggtc cagagatccc tgtggacagc caccgagaat tcctacctgg tcttagcggg 5160 cctcgccgat gggcttgtgg ctgtgtttcc cgtggtgcgg ggcaccccaa aggacagctg 5220 ctcctacctg tgctcacaca cagccaacag gtccaagttc agcatcgcgg atgaagacgc 5280 acggcagaac ccctacccag tgaaggccat ggaggtggtc aacagcggct ctgaggtctg 5340 gtacagcaat gggccgggcc tccttgtcat cgactgtgcc tccctggaga tctgcaggcg 5400 gctggagccc tacatggccc cctccatggt tacgtcagtc gtgtgcagct ctgagggcag 5460 aggggaggag gtcgtctggt gcctggatga caaggccaac tccttggtga tgtaccactc 5520 caccacctac cagctgtgtg cccggtactt ctgcggggtc cccagccccc tcagggacat 5580 gtttcccgtg cggcccttgg acacggaacc cccggcagcc agccacacgg ccaacccaaa 5640 ggtgcctgag ggggactcca tcgcggacgt gagcatcatg tacagtgagg agctgggcac 5700 gcagatcctg atccaccagg aatcactcac tgactactgc tccatgtcct cctactcctc 5760 atccccaccc cgccaggctg ccaggtcccc ctcaagcctc cccagctccc cagcaagttc 5820 ttccagtgtg cctttctcca ccgactgcga ggactcagac atgctacata cgcccggtgc 5880 tgcctccgac aggtctgagc atgacctgac ccccatggac ggggagacct tcagccagca 5940 cctgcaggcc gtgaagatcc tcgccgtcag agacctcatt tgggtcccca ggcgcggtgg 6000 agatgttatc gtcattggcc tggagaagga ttctggcgcc cagcggggcc gagtcattgc 6060 cgtcttaaaa gcccgagagc tgactccgca tggggtgctg gtggatgctg ccgtggtggc 6120 aaaggacact gttgtgtgca cctttgaaaa tgaaaacaca gagtggtgcc tggccgtctg 6180 gaggggctgg ggcgccaggg agttcgacat tttctaccag tcctacgagg agctgggccg 6240 gctggaggct tgcactcgca agagaaggta attcctgtgg aatgactgtc acacatcaga 6300 gctggctggc ccggggctgc agcctgactc ctctgccatc ggcctctagt tctccaagga 6360 cctagaagac agatggagtt ctcccctgaa ctccttgctg ctaagaagtg ctgagaagtt 6420 actcgcctgg cggtggctcc agggttctct ggttctctgg agcagagttc tctgaatacc 6480 ccatccccca actgctgatt ttacagcccc agggaagaca gtggtatcag gctgggagcg 6540 gcctcctctg gcctccccca tcagtttgca ggagcagggg tgcaggatcc tgttctgagc 6600 tgggtcaaac aaagcagggc cgggccttcc tgccatcccc aggtctcaga tggaattaca 6660 ctagaggccc tccgctggga agcacttgag gtagggcagg aggggggctg tgacccctgc 6720 cctttccccg ccagagacct caggctctca gcacattcca caggctcctg agtccccgag 6780 gcctgggcca gcttgggcaa gccaagatca gatgtctctg tgttcgggaa ggtctccgtg 6840 tgggaaagcc cttgggggat cccgggtgag gagtgttgcc ccatccagag aatgaatgag 6900 ttcctttaag tgccaccgcc agcaagccca gaggcacaca ttctgagtgc acccgcttag 6960 cctttacatt cctctccacc gacaaaagga aggggaaact caatcagcag gacttcagaa 7020 agggccttgt gtttatagct ttgtcaagta aatttggacg cagctggaaa cacaggcctg 7080 tttgttgcac ata 7093 2 2013 PRT Homo sapiens 2 Met Glu Thr Leu Asn Gly Ala Gly Asp Thr Gly Gly Lys Pro Ser Thr 1 5 10 15 Arg Gly Gly Asp Pro Ala Ala Arg Ser Arg Arg Thr Glu Gly Ile Arg 20 25 30 Ala Ala Tyr Arg Arg Gly Asp Arg Gly Gly Ala Arg Asp Leu Leu Glu 35 40 45 Glu Ala Cys Asp Gln Cys Ala Ser Gln Leu Glu Lys Gly Gln Leu Leu 50 55 60 Ser Ile Pro Ala Ala Tyr Gly Asp Leu Glu Met Val Arg Tyr Leu Leu 65 70 75 80 Ser Lys Arg Leu Val Glu Leu Pro Thr Glu Pro Thr Asp Asp Asn Pro 85 90 95 Ala Val Val Ala Ala Tyr Phe Gly His Thr Ala Val Val Gln Asn Thr 100 105 110 Leu Pro Thr Glu Pro Thr Asp Asp Asn Pro Ala Val Val Ala Ala Tyr 115 120 125 Phe Gly His Thr Ala Val Val Gln Glu Leu Leu Glu Ser Leu Pro Gly 130 135 140 Pro Cys Ser Pro Gln Arg Leu Leu Asn Trp Met Leu Ala Leu Ala Cys 145 150 155 160 Gln Arg Gly His Leu Gly Val Val Lys Leu Leu Val Leu Thr His Gly 165 170 175 Ala Asp Pro Glu Ser Tyr Ala Val Arg Lys Asn Glu Phe Pro Val Ile 180 185 190 Val Arg Leu Pro Leu Tyr Ala Ala Ile Lys Ser Gly Asn Glu Asp Ile 195 200 205 Ala Ile Phe Leu Leu Arg His Gly Ala Tyr Phe Cys Ser Tyr Ile Leu 210 215 220 Leu Asp Ser Pro Asp Pro Ser Lys His Leu Leu Arg Lys Tyr Phe Ile 225 230 235 240 Glu Ala Ser Pro Leu Pro Ser Ser Tyr Pro Gly Lys Thr Ala Leu Arg 245 250 255 Val Lys Trp Ser His Leu Arg Leu Pro Trp Val Asp Leu Asp Trp Leu 260 265 270 Ile Asp Ile Ser Cys Gln Ile Thr Glu Leu Asp Leu Ser Ala Asn Cys 275 280 285 Leu Ala Thr Leu Pro Ser Val Ile Pro Trp Gly Leu Ile Asn Leu Arg 290 295 300 Lys Leu Asn Leu Ser Asp Asn His Leu Gly Glu Leu Pro Gly Val Gln 305 310 315 320 Ser Ser Asp Glu Ile Ile Cys Ser Arg Leu Leu Glu Ile Asp Ile Ser 325 330 335 Ser Asn Lys Leu Ser His Leu Pro Pro Gly Phe Leu His Leu Ser Lys 340 345 350 Leu Gln Lys Leu Thr Ala Ser Lys Asn Cys Leu Glu Lys Leu Phe Glu 355 360 365 Glu Glu Asn Ala Thr Asn Trp Ile Gly Leu Arg Lys Leu Gln Glu Leu 370 375 380 Asp Ile Ser Asp Asn Lys Leu Thr Glu Leu Pro Ala Leu Phe Leu His 385 390 395 400 Ser Phe Lys Ser Leu Asn Ser Leu Asn Val Ser Arg Asn Asn Leu Lys 405 410 415 Val Phe Pro Asp Pro Trp Ala Cys Pro Leu Lys Cys Cys Lys Ala Ser 420 425 430 Arg Asn Ala Leu Glu Cys Leu Pro Asp Lys Met Ala Val Phe Trp Lys 435 440 445 Asn His Leu Lys Asp Val Asp Phe Ser Glu Asn Ala Leu Lys Glu Val 450 455 460 Pro Leu Gly Leu Phe Gln Leu Asp Ala Leu Met Phe Leu Arg Leu Gln 465 470 475 480 Gly Asn Gln Leu Ala Ala Leu Pro Pro Gln Glu Lys Trp Thr Cys Arg 485 490 495 Gln Leu Lys Thr Leu Asp Leu Ser Arg Asn Gln Leu Gly Lys Asn Glu 500 505 510 Asp Gly Leu Lys Thr Lys Arg Ile Ala Phe Phe Thr Thr Arg Gly Arg 515 520 525 Gln Arg Ser Gly Thr Glu Ala Glu Thr Thr Met Glu Phe Ser Ala Ser 530 535 540 Leu Val Thr Ile Val Phe Leu Ser Asn Asn Cys Asn Leu Cys Ala Tyr 545 550 555 560 Thr Cys Ala Ala Ser Val Leu Glu Phe Pro Ala Phe Leu Ser Glu Ser 565 570 575 Leu Glu Val Leu Cys Leu Asn Asp Asn His Leu Asp Thr Val Pro Pro 580 585 590 Ser Val Cys Leu Leu Lys Ser Leu Ser Glu Leu Tyr Leu Gly Asn Asn 595 600 605 Pro Gly Leu Arg Glu Leu Pro Pro Glu Leu Gly Gln Leu Gly Asn Leu 610 615 620 Trp Gln Leu Asp Thr Glu Asp Leu Thr Ile Ser Asn Val Pro Ala Glu 625 630 635 640 Ile Gln Lys Glu Gly Pro Lys Ala Met Leu Ser Tyr Leu Arg Ala Gln 645 650 655 Leu Arg Lys Ala Glu Lys Cys Lys Leu Met Lys Met Ile Ile Val Gly 660 665 670 Pro Pro Arg Gln Gly Lys Ser Thr Leu Leu Glu Ile Leu Gln Thr Gly 675 680 685 Arg Ala Pro Gln Val Val His Gly Glu Ala Thr Ile Arg Thr Thr Lys 690 695 700 Trp Glu Leu Gln Arg Pro Ala Gly Ser Arg Ala Lys Val Lys Asp Gly 705 710 715 720 Leu Arg Ala Glu Ser Leu Trp Val Glu Ser Val Glu Phe Asn Val Trp 725 730 735 Asp Ile Gly Gly Pro Ala Ser Met Ala Thr Val Asn Gln Cys Phe Phe 740 745 750 Thr Asp Lys Ala Leu Tyr Val Val Val Trp Asn Leu Ala Leu Gly Glu 755 760 765 Glu Ala Val Ala Asn Leu Gln Phe Trp Leu Leu Asn Ile Glu Ala Lys 770 775 780 Ala Pro Asn Ala Val Val Leu Val Val Gly Thr His Leu Asp Leu Ile 785 790 795 800 Glu Ala Lys Phe Arg Val Glu Arg Ile Ala Thr Leu Arg Ala Tyr Val 805 810 815 Leu Ala Leu Cys Arg Ser Pro Ser Gly Ser Arg Ala Thr Gly Phe Pro 820 825 830 Asp Ile Thr Phe Lys His Leu His Glu Ile Ser Cys Lys Ser Leu Glu 835 840 845 Gly Gln Glu Gly Leu Arg Gln Leu Ile Phe His Val Thr Cys Ser Met 850 855 860 Lys Asp Val Gly Ser Thr Ile Gly Cys Gln Arg Leu Ala Gly Arg Leu 865 870 875 880 Ile Pro Arg Ser Tyr Leu Ser Leu Gln Glu Ala Val Leu Ala Glu Gln 885 890 895 Gln Arg Arg Ser Arg Asp Asp Asp Val Gln Tyr Leu Thr Asp Arg Gln 900 905 910 Leu Glu Gln Leu Val Glu Gln Thr Pro Asp Asn Asp Ile Lys Asp Tyr 915 920 925 Glu Asp Leu Gln Ser Ala Ile Ser Phe Leu Ile Glu Thr Gly Thr Leu 930 935 940 Leu His Phe Pro Asp Thr Ser His Gly Leu Arg Asn Leu Tyr Phe Leu 945 950 955 960 Asp Pro Ile Trp Leu Ser Glu Cys Leu Gln Arg Ile Phe Asn Ile Lys 965 970 975 Gly Ser Arg Ser Val Ala Lys Asn Gly Val Ile Arg Ala Glu Asp Leu 980 985 990 Arg Met Leu Leu Val Gly Thr Gly Phe Thr Gln Gln Thr Glu Glu Gln 995 1000 1005 Tyr Phe Gln Phe Leu Ala Lys Phe Glu Ile Ala Leu Pro Val Ala Asn 1010 1015 1020 Asp Ser Tyr Leu Leu Pro His Leu Leu Pro Ser Lys Pro Gly Leu Asp 1025 1030 1035 1040 Thr His Gly Met Arg His Pro Thr Ala Asn Thr Ile Gln Arg Val Phe 1045 1050 1055 Lys Met Ser Phe Val Pro Val Gly Phe Trp Gln Arg Phe Ile Ala Arg 1060 1065 1070 Met Leu Ile Ser Leu Ala Glu Met Asp Leu Gln Leu Phe Glu Asn Lys 1075 1080 1085 Lys Asn Thr Lys Ser Arg Asn Arg Lys Val Thr Ile Tyr Ser Phe Thr 1090 1095 1100 Gly Asn Gln Arg Asn Arg Cys Ser Thr Phe Arg Val Lys Arg Asn Gln 1105 1110 1115 1120 Thr Ile Tyr Trp Gln Glu Gly Leu Leu Val Thr Phe Asp Gly Gly Tyr 1125 1130 1135 Leu Ser Val Glu Ser Ser Asp Val Asn Trp Lys Lys Lys Lys Ser Gly 1140 1145 1150 Gly Met Lys Ile Val Cys Gln Ser Glu Val Arg Asp Phe Ser Ala Met 1155 1160 1165 Ala Phe Ile Thr Asp His Val Asn Ser Leu Ile Asp Gln Trp Phe Pro 1170 1175 1180 Ala Leu Thr Ala Thr Glu Ser Asp Gly Thr Pro Leu Met Glu Gln Tyr 1185 1190 1195 1200 Val Pro Cys Pro Val Cys Glu Thr Ala Trp Ala Gln His Thr Asp Pro 1205 1210 1215 Ser Glu Lys Ser Glu Asp Val Gln Tyr Phe Asp Met Glu Asp Cys Val 1220 1225 1230 Leu Thr Ala Ile Glu Arg Asp Phe Ile Ser Cys Pro Arg His Pro Asp 1235 1240 1245 Leu Pro Val Pro Leu Gln Glu Leu Val Pro Glu Leu Phe Met Thr Asp 1250 1255 1260 Phe Pro Ala Arg Leu Phe Leu Glu Asn Ser Lys Leu Glu His Ser Glu 1265 1270 1275 1280 Asp Glu Gly Ser Val Leu Gly Gln Gly Gly Ser Gly Thr Val Ile Tyr 1285 1290 1295 Arg Ala Arg Tyr Gln Gly Gln Pro Val Ala Val Lys Arg Phe His Ile 1300 1305 1310 Lys Lys Phe Lys Asn Phe Ala Asn Val Pro Ala Asp Thr Met Leu Arg 1315 1320 1325 His Leu Arg Ala Thr Asp Ala Met Lys Asn Phe Ser Glu Phe Arg Gln 1330 1335 1340 Glu Ala Ser Met Leu His Ala Leu Gln His Pro Cys Ile Val Ala Leu 1345 1350 1355 1360 Ile Gly Ile Ser Ile His Pro Leu Cys Phe Ala Leu Glu Leu Ala Pro 1365 1370 1375 Leu Ser Ser Leu Asn Thr Val Leu Ser Glu Asn Ala Arg Asp Ser Ser 1380 1385 1390 Phe Ile Pro Leu Gly His Met Leu Thr Gln Lys Ile Ala Tyr Gln Ile 1395 1400 1405 Ala Ser Gly Leu Ala Tyr Leu His Lys Lys Asn Ile Ile Phe Cys Asp 1410 1415 1420 Leu Lys Ser Asp Asn Ile Leu Val Trp Ser Leu Asp Val Lys Glu His 1425 1430 1435 1440 Ile Asn Ile Lys Leu Ser Asp Tyr Gly Ile Ser Arg Gln Ser Phe His 1445 1450 1455 Glu Gly Ala Leu Gly Val Glu Gly Thr Pro Gly Tyr Gln Ala Pro Glu 1460 1465 1470 Ile Arg Pro Arg Ile Val Tyr Asp Glu Lys Val Asp Met Phe Ser Tyr 1475 1480 1485 Gly Met Val Leu Tyr Glu Leu Leu Ser Gly Gln Arg Pro Ala Leu Gly 1490 1495 1500 His His Gln Leu Gln Ile Ala Lys Lys Leu Ser Lys Gly Ile Arg Pro 1505 1510 1515 1520 Val Leu Gly Gln Pro Glu Glu Val Gln Phe Arg Arg Leu Gln Ala Leu 1525 1530 1535 Met Met Glu Cys Trp Asp Thr Lys Pro Glu Lys Arg Pro Leu Ala Leu 1540 1545 1550 Ser Val Val Ser Gln Met Lys Asp Pro Thr Phe Ala Thr Phe Met Tyr 1555 1560 1565 Glu Leu Cys Cys Gly Lys Gln Thr Ala Phe Phe Ser Ser Gln Gly Gln 1570 1575 1580 Glu Tyr Thr Val Val Phe Trp Asp Gly Lys Glu Glu Ser Arg Asn Tyr 1585 1590 1595 1600 Thr Val Val Asn Thr Glu Lys Gly Leu Met Glu Val Gln Arg Met Cys 1605 1610 1615 Cys Pro Gly Met Lys Val Ser Cys Gln Leu Gln Val Gln Arg Ser Leu 1620 1625 1630 Trp Thr Ala Thr Glu Asn Ser Tyr Leu Val Leu Ala Gly Leu Ala Asp 1635 1640 1645 Gly Leu Val Ala Val Phe Pro Val Val Arg Gly Thr Pro Lys Asp Ser 1650 1655 1660 Cys Ser Tyr Leu Cys Ser His Thr Ala Asn Arg Ser Lys Phe Ser Ile 1665 1670 1675 1680 Ala Asp Glu Asp Ala Arg Gln Asn Pro Tyr Pro Val Lys Ala Met Glu 1685 1690 1695 Val Val Asn Ser Gly Ser Glu Val Trp Tyr Ser Asn Gly Pro Gly Leu 1700 1705 1710 Leu Val Ile Asp Cys Ala Ser Leu Glu Ile Cys Arg Arg Leu Glu Pro 1715 1720 1725 Tyr Met Ala Pro Ser Met Val Thr Ser Val Val Cys Ser Ser Glu Gly 1730 1735 1740 Arg Gly Glu Glu Val Val Trp Cys Leu Asp Asp Lys Ala Asn Ser Leu 1745 1750 1755 1760 Val Met Tyr His Ser Thr Thr Tyr Gln Leu Cys Ala Arg Tyr Phe Cys 1765 1770 1775 Gly Val Pro Ser Pro Leu Arg Asp Met Phe Pro Val Arg Pro Leu Asp 1780 1785 1790 Thr Glu Pro Pro Ala Ala Ser His Thr Ala Asn Pro Lys Val Pro Glu 1795 1800 1805 Gly Asp Ser Ile Ala Asp Val Ser Ile Met Tyr Ser Glu Glu Leu Gly 1810 1815 1820 Thr Gln Ile Leu Ile His Gln Glu Ser Leu Thr Asp Tyr Cys Ser Met 1825 1830 1835 1840 Ser Ser Tyr Ser Ser Ser Pro Pro Arg Gln Ala Ala Arg Ser Pro Ser 1845 1850 1855 Ser Leu Pro Ser Ser Pro Ala Ser Ser Ser Ser Val Pro Phe Ser Thr 1860 1865 1870 Asp Cys Glu Asp Ser Asp Met Leu His Thr Pro Gly Ala Ala Ser Asp 1875 1880 1885 Arg Ser Glu His Asp Leu Thr Pro Met Asp Gly Glu Thr Phe Ser Gln 1890 1895 1900 His Leu Gln Ala Val Lys Ile Leu Ala Val Arg Asp Leu Ile Trp Val 1905 1910 1915 1920 Pro Arg Arg Gly Gly Asp Val Ile Val Ile Gly Leu Glu Lys Asp Ser 1925 1930 1935 Gly Ala Gln Arg Gly Arg Val Ile Ala Val Leu Lys Ala Arg Glu Leu 1940 1945 1950 Thr Pro His Gly Val Leu Val Asp Ala Ala Val Val Ala Lys Asp Thr 1955 1960 1965 Val Val Cys Thr Phe Glu Asn Glu Asn Thr Glu Trp Cys Leu Ala Val 1970 1975 1980 Trp Arg Gly Trp Gly Ala Arg Glu Phe Asp Ile Phe Tyr Gln Ser Tyr 1985 1990 1995 2000 Glu Glu Leu Gly Arg Leu Glu Ala Cys Thr Arg Lys Arg 2005 2010 3 7307 DNA Homo sapiens 3 gcggccgccg aggggacgcc tcgtgacggt tcctgggaga gctggcggcg gccttgctct 60 gcgcgctctt cgcgccgccc tccccgcccg cccgcctcag gattgaggaa gtgcgtctgg 120 gcccggcccc ggcgcggggg gcagacggcg gtgggacggc caggccccgg ccccgccagt 180 gtgtccgccc ggccccgcgt cccggagcgc ccgcacccgg ccccgccgcc gcctcagagc 240 aagaaagctt tctgctcagc catggctacg agtccacgcc ttaatgcacc ccacagccag 300 cggcagtggc agtgacaaca gcgggacctg cctttgaaga tcggctgctg caagggttga 360 tggctggcat gtcgcaaaga ccccccagca tgtactggtg tgtggggccg gaggagtcag 420 ctgtgtgtcc agaacgtgcc atggagacgc ttaacggtgc cggggacacg ggcggcaagc 480 cgtccacgcg gggcggtgac cctgcagcgc ggtcccgcag gacggaaggc atccgcgccg 540 cgtacaggcg gggagaccgc ggcggcgccc gggacctgct ggaggaggcc tgcgaccagt 600 gcgcgtccca gctggaaaag ggccagcttc tgagcatccc ggcagcctat ggggatctgg 660 agatggtccg ctacctactc agcaagagac tggtggagct gcccaccgag cccacggatg 720 acaacccagc cgtggtggca gcgtattttg gacacacggc agttgtgcaa aatacgctgc 780 ccaccgagcc cacggatgac aacccagccg tggtggcagc gtattttgga cacacggcag 840 ttgtgcagga attgcttgag tccttaccag gtccctgcag tccccagcgg cttctgaact 900 ggatgctggc cttggcttgc cagcgagggc acctgggggt tgtgaagctc ctggtcctga 960 cgcacggggc tgacccggag agctacgctg tcaggaagaa tgagttccct gtcatcgtgc 1020 gcttgcccct gtatgcggcc atcaagtcag ggaatgaaga cattgcaata ttcctgcttc 1080 ggcatggggc ctatttctgt tcctacatct tgctggatag tcctgacccc agcaaacatc 1140 tgctgagaaa gtacttcatt gaagccagtc ccttgcccag cagttatccg ggaaaaacag 1200 ctctccgtgt gaaatggtcc catctcagac tgccctgggt agacctagac tggctcatag 1260 acatctcctg ccagatcacg gagctcgacc tttctgccaa ctgcctggcg accctcccct 1320 cggttatccc ctggggcctc atcaatctcc ggaagctgaa cctctccgac aaccacctgg 1380 gggagctgcc tggcgtgcag tcatcggacg aaatcatctg ttccaggcta cttgaaattg 1440 acatttccag caacaagttg tcccacctcc ctcctggatt cttgcacctc tcaaaacttc 1500 aaaaactgac agcttcaaaa aattgtttag aaaaattgtt cgaagaagaa aatgccacta 1560 actggatagg tttacggaag ctacaggaac ttgatatatc tgacaataaa ttgacagaac 1620 tccctgccct gttccttcac tctttcaagt ccctcaattc tctgaatgtc tccagaaaca 1680 acctgaaggt gtttccagat ccctgggcct gccctttgaa atgttgtaaa gcttccagaa 1740 atgccctgga atgtctgcca gacaaaatgg ctgtcttttg gaaaaatcac ctgaaggatg 1800 tggatttctc agaaaacgca ctcaaagaag ttcccctggg acttttccag cttgatgccc 1860 tcatgttctt gaggttacag gggaaccagc tggcggcact tccacctcaa gagaagtgga 1920 cctgcaggca gctcaaaacc ctggatctct ccagaaacca acttggcaaa aatgaagatg 1980 gactgaaaac gaagcgtatt gcctttttca ccaccagagg tcgccagcgc tccgggactg 2040 aggcagagac aactatggag ttcagtgcat ctctggtaac cattgtgttc ctgtctaaca 2100 actgtaacct ctgtgcatac acatgtgcag caagtgtgct ggaatttccg gccttcctaa 2160 gtgagtcttt ggaagtcctt tgcctgaacg acaaccacct cgacacagtc cctccctcgg 2220 tttgcctact gaagagctta tcagagctct acttgggaaa caaccctggc ctccgggagc 2280 tccctcctga gctggggcag ctgggcaacc tctggcagct ggacactgaa gacctgacca 2340 tcagcaatgt gcctgcagaa atccaaaaag aaggccccaa agcaatgctg tcttacctgc 2400 gtgctcagct gcggaaagcg gaaaagtgca agctgatgaa gatgatcatc gtgggtcccc 2460 cgcgccaggg caagtccacc ctcctggaga tcttacagac ggggagggcc ccccaggtgg 2520 tgcatggaga ggccaccatc aggaccacca agtgggagct ccagaggccg gctggctcga 2580 gagccaaggt caaggatggt ctgcgtgcag agtccctgtg ggttgagtcc gtggagttca 2640 acgtctggga catcggggga ccggccagca tggccactgt caaccagtgc ttcttcacgg 2700 acaaggccct gtacgtggtg gtctggaacc tggcgctggg ggaggaggcc gtggccaacc 2760 tccagttctg gctgctcaac atcgaggcca aggccccaaa cgccgtggtg ctggtggtcg 2820 ggacgcacct ggatttaatt gaagccaagt tccgtgtgga aaggattgca acgctgcgtg 2880 cctatgtgct ggcactctgc cgctccccct ccggctccag ggccacaggc ttcccagaca 2940 tcaccttcaa acacttacat gagatttcct gcaagagcct ggaaggtcag gaagggctgc 3000 gacagctgat tttccacgtc acgtgcagca tgaaggacgt cggcagcacc atcggctgcc 3060 agcgactggc agggcggctg atccccagga gctacctgag cctgcaggag gccgtgctgg 3120 cagagcagca gcgccgcagc cgggacgacg acgtgcagta cctgacggac aggcagctgg 3180 agcagctggt ggagcagacg cccgacaacg acatcaagga ctacgaggac ctgcagtcag 3240 ccatcagctt cctcatagaa accggcaccc tgctccattt cccggacacc agccacggcc 3300 tgaggaacct ctacttcctc gaccctattt ggctctccga atgtctgcag aggatcttta 3360 atattaaggg ctctcggtca gtggccaaga atggggtgat cagagcagaa gacctcagga 3420 tgctgctggt ggggactggc ttcacgcagc agacggaaga gcagtacttc cagttcctgg 3480 ccaagtttga gatcgccctg cccgtcgcca atgacagcta cctcctgccc catctccttc 3540 catctaaacc tggcctggac acccacggta tgcggcaccc cacagccaac accattcaga 3600 gggtatttaa gatgagcttc gttcccgttg gcttctggca aaggtttata gcacggatgc 3660 tgatcagcct ggcggagatg gacctgcagc tttttgaaaa caagaagaat actaaaagca 3720 ggaacaggaa agtcaccatt tacagtttta caggaaacca gagaaatcgc tgtagcacat 3780 tcagagtgaa aagaaatcag accatctatt ggcaggaagg gctcctggtc acttttgatg 3840 ggggctacct cagtgtggaa tcttccgacg tgaactggaa aaagaagaaa agcggaggaa 3900 tgaaaattgt ttgccaatca gaagtgaggg acttctcagc catggctttc atcacggacc 3960 acgtcaattc cttgattgat cagtggtttc ccgccctgac agccacagag agcgacggga 4020 cgccactcat ggagcagtac gtgccctgcc cggtctgcga gacagcctgg gcccagcaca 4080 cggaccccag tgagaaatca gaggatgtgc agtacttcga catggaagac tgtgtcctga 4140 cggccatcga gcgggacttc atctcctgcc ccagacaccc ggacctcccc gtgccgctgc 4200 aggagctggt ccctgaactg ttcatgaccg acttcccggc caggctcttc ctggagaaca 4260 gcaagctgga gcacagcgag gacgagggca gcgtcctggg ccagggcggc agtggcaccg 4320 tcatctaccg ggcccggtac cagggccagc ctgtggccgt caagcgcttc cacatcaaaa 4380 aattcaagaa ctttgctaac gtaccggcag acaccatgct gaggcacctg cgggccaccg 4440 atgccatgaa gaacttctcc gagttccggc aggaggccag catgctgcac gcgctgcagc 4500 acccctgcat cgtggcgctc atcggcatca gcatccaccc gctctgcttc gccctggagc 4560 tcgcgccgct cagcagcctc aacaccgtgc tgtccgagaa cgccagagat tcttccttta 4620 tacccctggg acacatgctc acccaaaaaa tagcctacca gatcgcctcg ggcctggcct 4680 acctgcacaa gaaaaacatc atcttctgtg acctgaagtc ggacaacatt ctggtgtggt 4740 cccttgacgt caaggagcac atcaacatca agctatctga ctacgggatt tcgaggcagt 4800 cattccatga gggcgcccta ggcgtggagg gcactcctgg ctaccaggcc ccagagatca 4860 ggcctcgcat tgtatatgat gagaaggtag atatgttctc ctatggaatg gtgctctacg 4920 agttgctgtc aggacagcgc cctgcactgg gccaccacca gctccagatt gccaagaagc 4980 tgtccaaggg catccgcccg gttctggggc agccggagga agtgcagttc cggcgactgc 5040 aggcgctcat gatggagtgc tgggacacta agccagagaa gcgaccgctg gccctgtcgg 5100 tggtgagcca gatgaaggac ccgacttttg ccaccttcat gtatgaactg tgctgtggga 5160 agcagacagc cttcttctca tcccagggcc aggagtacac cgtggtgttt tgggatggaa 5220 aagaggagtc caggaactac acggtggtga acacagagaa gggcctcatg gaggtgcaga 5280 ggatgtgctg ccctgggatg aaggtgagct gccagctcca ggtccagaga tccctgtgga 5340 cagccaccga gaattcctac ctggtcttag cgggcctcgc cgatgggctt gtggctgtgt 5400 ttcccgtggt gcggggcacc ccaaaggaca gctgctccta cctgtgctca cacacagcca 5460 acaggtccaa gttcagcatc gcggatgaag acgcacggca gaacccctac ccagtgaagg 5520 ccatggaggt ggtcaacagc ggctctgagg tctggtacag caatgggccg ggcctccttg 5580 tcatcgactg tgcctccctg gagatctgca ggcggctgga gccctacatg gccccctcca 5640 tggttacgtc agtcgtgtgc agctctgagg gcagagggga ggaggtcgtc tggtgcctgg 5700 atgacaaggc caactccttg gtgatgtacc actccaccac ctaccagctg tgtgcccggt 5760 acttctgcgg ggtccccagc cccctcaggg acatgtttcc cgtgcggccc ttggacacgg 5820 aacccccggc agccagccac acggccaacc caaaggtgcc tgagggggac tccatcgcgg 5880 acgtgagcat catgtacagt gaggagctgg gcacgcagat cctgatccac caggaatcac 5940 tcactgacta ctgctccatg tcctcctact cctcatcccc accccgccag gctgccaggt 6000 ccccctcaag cctccccagc tccccagcaa gttcttccag tgtgcctttc tccaccgact 6060 gcgaggactc agacatgcta catacgcccg gtgctgcctc cgacaggtct gagcatgacc 6120 tgacccccat ggacggggag accttcagcc agcacctgca ggccgtgaag atcctcgccg 6180 tcagagacct catttgggtc cccaggcgcg gtggagatgt tatcgtcatt ggcctggaga 6240 aggattctgg cgcccagcgg ggccgagtca ttgccgtctt aaaagcccga gagctgactc 6300 cgcatggggt gctggtggat gctgccgtgg tggcaaagga cactgttgtg tgcacctttg 6360 aaaatgaaaa cacagagtgg tgcctggccg tctggagggg ctggggcgcc agggagttcg 6420 acattttcta ccagtcctac gaggagctgg gccggctgga ggcttgcact cgcaagagaa 6480 ggtaattcct gtggaatgac tgtcacacat cagagctggc tggcccgggg ctgcagcctg 6540 actcctctgc catcggcctc tagttctcca aggacctaga agacagatgg agttctcccc 6600 tgaactcctt gctgctaaga agtgctgaga agttactcgc ctggcggtgg ctccagggtt 6660 ctctggttct ctggagcaga gttctctgaa taccccatcc cccaactgct gattttacag 6720 ccccagggaa gacagtggta tcaggctggg agcggcctcc tctggcctcc cccatcagtt 6780 tgcaggagca ggggtgcagg atcctgttct gagctgggtc aaacaaagca gggccgggcc 6840 ttcctgccat ccccaggtct cagatggaat tacactagag gccctccgct gggaagcact 6900 tgaggtaggg caggaggggg gctgtgaccc ctgccctttc cccgccagag acctcaggct 6960 ctcagcacat tccacaggct cctgagtccc cgaggcctgg gccagcttgg gcaagccaag 7020 atcagatgtc tctgtgttcg ggaaggtctc cgtgtgggaa agcccttggg ggatcccggg 7080 tgaggagtgt tgccccatcc agagaatgaa tgagttcctt taagtgccac cgccagcaag 7140 cccagaggca cacattctga gtgcacccgc ttagccttta cattcctctc caccgacaaa 7200 aggaagggga aactcaatca gcaggacttc agaaagggcc ttgtgtttat agctttgtca 7260 agtaaatttg gacgcagctg gaaacacagg cctgtttgtt gcacata 7307 4 2040 PRT Homo sapiens 4 Met Ala Gly Met Ser Gln Arg Pro Pro Ser Met Tyr Trp Cys Val Gly 1 5 10 15 Pro Glu Glu Ser Ala Val Cys Pro Glu Arg Ala Met Glu Thr Leu Asn 20 25 30 Gly Ala Gly Asp Thr Gly Gly Lys Pro Ser Thr Arg Gly Gly Asp Pro 35 40 45 Ala Ala Arg Ser Arg Arg Thr Glu Gly Ile Arg Ala Ala Tyr Arg Arg 50 55 60 Gly Asp Arg Gly Gly Ala Arg Asp Leu Leu Glu Glu Ala Cys Asp Gln 65 70 75 80 Cys Ala Ser Gln Leu Glu Lys Gly Gln Leu Leu Ser Ile Pro Ala Ala 85 90 95 Tyr Gly Asp Leu Glu Met Val Arg Tyr Leu Leu Ser Lys Arg Leu Val 100 105 110 Glu Leu Pro Thr Glu Pro Thr Asp Asp Asn Pro Ala Val Val Ala Ala 115 120 125 Tyr Phe Gly His Thr Ala Val Val Gln Asn Thr Leu Pro Thr Glu Pro 130 135 140 Thr Asp Asp Asn Pro Ala Val Val Ala Ala Tyr Phe Gly His Thr Ala 145 150 155 160 Val Val Gln Glu Leu Leu Glu Ser Leu Pro Gly Pro Cys Ser Pro Gln 165 170 175 Arg Leu Leu Asn Trp Met Leu Ala Leu Ala Cys Gln Arg Gly His Leu 180 185 190 Gly Val Val Lys Leu Leu Val Leu Thr His Gly Ala Asp Pro Glu Ser 195 200 205 Tyr Ala Val Arg Lys Asn Glu Phe Pro Val Ile Val Arg Leu Pro Leu 210 215 220 Tyr Ala Ala Ile Lys Ser Gly Asn Glu Asp Ile Ala Ile Phe Leu Leu 225 230 235 240 Arg His Gly Ala Tyr Phe Cys Ser Tyr Ile Leu Leu Asp Ser Pro Asp 245 250 255 Pro Ser Lys His Leu Leu Arg Lys Tyr Phe Ile Glu Ala Ser Pro Leu 260 265 270 Pro Ser Ser Tyr Pro Gly Lys Thr Ala Leu Arg Val Lys Trp Ser His 275 280 285 Leu Arg Leu Pro Trp Val Asp Leu Asp Trp Leu Ile Asp Ile Ser Cys 290 295 300 Gln Ile Thr Glu Leu Asp Leu Ser Ala Asn Cys Leu Ala Thr Leu Pro 305 310 315 320 Ser Val Ile Pro Trp Gly Leu Ile Asn Leu Arg Lys Leu Asn Leu Ser 325 330 335 Asp Asn His Leu Gly Glu Leu Pro Gly Val Gln Ser Ser Asp Glu Ile 340 345 350 Ile Cys Ser Arg Leu Leu Glu Ile Asp Ile Ser Ser Asn Lys Leu Ser 355 360 365 His Leu Pro Pro Gly Phe Leu His Leu Ser Lys Leu Gln Lys Leu Thr 370 375 380 Ala Ser Lys Asn Cys Leu Glu Lys Leu Phe Glu Glu Glu Asn Ala Thr 385 390 395 400 Asn Trp Ile Gly Leu Arg Lys Leu Gln Glu Leu Asp Ile Ser Asp Asn 405 410 415 Lys Leu Thr Glu Leu Pro Ala Leu Phe Leu His Ser Phe Lys Ser Leu 420 425 430 Asn Ser Leu Asn Val Ser Arg Asn Asn Leu Lys Val Phe Pro Asp Pro 435 440 445 Trp Ala Cys Pro Leu Lys Cys Cys Lys Ala Ser Arg Asn Ala Leu Glu 450 455 460 Cys Leu Pro Asp Lys Met Ala Val Phe Trp Lys Asn His Leu Lys Asp 465 470 475 480 Val Asp Phe Ser Glu Asn Ala Leu Lys Glu Val Pro Leu Gly Leu Phe 485 490 495 Gln Leu Asp Ala Leu Met Phe Leu Arg Leu Gln Gly Asn Gln Leu Ala 500 505 510 Ala Leu Pro Pro Gln Glu Lys Trp Thr Cys Arg Gln Leu Lys Thr Leu 515 520 525 Asp Leu Ser Arg Asn Gln Leu Gly Lys Asn Glu Asp Gly Leu Lys Thr 530 535 540 Lys Arg Ile Ala Phe Phe Thr Thr Arg Gly Arg Gln Arg Ser Gly Thr 545 550 555 560 Glu Ala Glu Thr Thr Met Glu Phe Ser Ala Ser Leu Val Thr Ile Val 565 570 575 Phe Leu Ser Asn Asn Cys Asn Leu Cys Ala Tyr Thr Cys Ala Ala Ser 580 585 590 Val Leu Glu Phe Pro Ala Phe Leu Ser Glu Ser Leu Glu Val Leu Cys 595 600 605 Leu Asn Asp Asn His Leu Asp Thr Val Pro Pro Ser Val Cys Leu Leu 610 615 620 Lys Ser Leu Ser Glu Leu Tyr Leu Gly Asn Asn Pro Gly Leu Arg Glu 625 630 635 640 Leu Pro Pro Glu Leu Gly Gln Leu Gly Asn Leu Trp Gln Leu Asp Thr 645 650 655 Glu Asp Leu Thr Ile Ser Asn Val Pro Ala Glu Ile Gln Lys Glu Gly 660 665 670 Pro Lys Ala Met Leu Ser Tyr Leu Arg Ala Gln Leu Arg Lys Ala Glu 675 680 685 Lys Cys Lys Leu Met Lys Met Ile Ile Val Gly Pro Pro Arg Gln Gly 690 695 700 Lys Ser Thr Leu Leu Glu Ile Leu Gln Thr Gly Arg Ala Pro Gln Val 705 710 715 720 Val His Gly Glu Ala Thr Ile Arg Thr Thr Lys Trp Glu Leu Gln Arg 725 730 735 Pro Ala Gly Ser Arg Ala Lys Val Lys Asp Gly Leu Arg Ala Glu Ser 740 745 750 Leu Trp Val Glu Ser Val Glu Phe Asn Val Trp Asp Ile Gly Gly Pro 755 760 765 Ala Ser Met Ala Thr Val Asn Gln Cys Phe Phe Thr Asp Lys Ala Leu 770 775 780 Tyr Val Val Val Trp Asn Leu Ala Leu Gly Glu Glu Ala Val Ala Asn 785 790 795 800 Leu Gln Phe Trp Leu Leu Asn Ile Glu Ala Lys Ala Pro Asn Ala Val 805 810 815 Val Leu Val Val Gly Thr His Leu Asp Leu Ile Glu Ala Lys Phe Arg 820 825 830 Val Glu Arg Ile Ala Thr Leu Arg Ala Tyr Val Leu Ala Leu Cys Arg 835 840 845 Ser Pro Ser Gly Ser Arg Ala Thr Gly Phe Pro Asp Ile Thr Phe Lys 850 855 860 His Leu His Glu Ile Ser Cys Lys Ser Leu Glu Gly Gln Glu Gly Leu 865 870 875 880 Arg Gln Leu Ile Phe His Val Thr Cys Ser Met Lys Asp Val Gly Ser 885 890 895 Thr Ile Gly Cys Gln Arg Leu Ala Gly Arg Leu Ile Pro Arg Ser Tyr 900 905 910 Leu Ser Leu Gln Glu Ala Val Leu Ala Glu Gln Gln Arg Arg Ser Arg 915 920 925 Asp Asp Asp Val Gln Tyr Leu Thr Asp Arg Gln Leu Glu Gln Leu Val 930 935 940 Glu Gln Thr Pro Asp Asn Asp Ile Lys Asp Tyr Glu Asp Leu Gln Ser 945 950 955 960 Ala Ile Ser Phe Leu Ile Glu Thr Gly Thr Leu Leu His Phe Pro Asp 965 970 975 Thr Ser His Gly Leu Arg Asn Leu Tyr Phe Leu Asp Pro Ile Trp Leu 980 985 990 Ser Glu Cys Leu Gln Arg Ile Phe Asn Ile Lys Gly Ser Arg Ser Val 995 1000 1005 Ala Lys Asn Gly Val Ile Arg Ala Glu Asp Leu Arg Met Leu Leu Val 1010 1015 1020 Gly Thr Gly Phe Thr Gln Gln Thr Glu Glu Gln Tyr Phe Gln Phe Leu 1025 1030 1035 1040 Ala Lys Phe Glu Ile Ala Leu Pro Val Ala Asn Asp Ser Tyr Leu Leu 1045 1050 1055 Pro His Leu Leu Pro Ser Lys Pro Gly Leu Asp Thr His Gly Met Arg 1060 1065 1070 His Pro Thr Ala Asn Thr Ile Gln Arg Val Phe Lys Met Ser Phe Val 1075 1080 1085 Pro Val Gly Phe Trp Gln Arg Phe Ile Ala Arg Met Leu Ile Ser Leu 1090 1095 1100 Ala Glu Met Asp Leu Gln Leu Phe Glu Asn Lys Lys Asn Thr Lys Ser 1105 1110 1115 1120 Arg Asn Arg Lys Val Thr Ile Tyr Ser Phe Thr Gly Asn Gln Arg Asn 1125 1130 1135 Arg Cys Ser Thr Phe Arg Val Lys Arg Asn Gln Thr Ile Tyr Trp Gln 1140 1145 1150 Glu Gly Leu Leu Val Thr Phe Asp Gly Gly Tyr Leu Ser Val Glu Ser 1155 1160 1165 Ser Asp Val Asn Trp Lys Lys Lys Lys Ser Gly Gly Met Lys Ile Val 1170 1175 1180 Cys Gln Ser Glu Val Arg Asp Phe Ser Ala Met Ala Phe Ile Thr Asp 1185 1190 1195 1200 His Val Asn Ser Leu Ile Asp Gln Trp Phe Pro Ala Leu Thr Ala Thr 1205 1210 1215 Glu Ser Asp Gly Thr Pro Leu Met Glu Gln Tyr Val Pro Cys Pro Val 1220 1225 1230 Cys Glu Thr Ala Trp Ala Gln His Thr Asp Pro Ser Glu Lys Ser Glu 1235 1240 1245 Asp Val Gln Tyr Phe Asp Met Glu Asp Cys Val Leu Thr Ala Ile Glu 1250 1255 1260 Arg Asp Phe Ile Ser Cys Pro Arg His Pro Asp Leu Pro Val Pro Leu 1265 1270 1275 1280 Gln Glu Leu Val Pro Glu Leu Phe Met Thr Asp Phe Pro Ala Arg Leu 1285 1290 1295 Phe Leu Glu Asn Ser Lys Leu Glu His Ser Glu Asp Glu Gly Ser Val 1300 1305 1310 Leu Gly Gln Gly Gly Ser Gly Thr Val Ile Tyr Arg Ala Arg Tyr Gln 1315 1320 1325 Gly Gln Pro Val Ala Val Lys Arg Phe His Ile Lys Lys Phe Lys Asn 1330 1335 1340 Phe Ala Asn Val Pro Ala Asp Thr Met Leu Arg His Leu Arg Ala Thr 1345 1350 1355 1360 Asp Ala Met Lys Asn Phe Ser Glu Phe Arg Gln Glu Ala Ser Met Leu 1365 1370 1375 His Ala Leu Gln His Pro Cys Ile Val Ala Leu Ile Gly Ile Ser Ile 1380 1385 1390 His Pro Leu Cys Phe Ala Leu Glu Leu Ala Pro Leu Ser Ser Leu Asn 1395 1400 1405 Thr Val Leu Ser Glu Asn Ala Arg Asp Ser Ser Phe Ile Pro Leu Gly 1410 1415 1420 His Met Leu Thr Gln Lys Ile Ala Tyr Gln Ile Ala Ser Gly Leu Ala 1425 1430 1435 1440 Tyr Leu His Lys Lys Asn Ile Ile Phe Cys Asp Leu Lys Ser Asp Asn 1445 1450 1455 Ile Leu Val Trp Ser Leu Asp Val Lys Glu His Ile Asn Ile Lys Leu 1460 1465 1470 Ser Asp Tyr Gly Ile Ser Arg Gln Ser Phe His Glu Gly Ala Leu Gly 1475 1480 1485 Val Glu Gly Thr Pro Gly Tyr Gln Ala Pro Glu Ile Arg Pro Arg Ile 1490 1495 1500 Val Tyr Asp Glu Lys Val Asp Met Phe Ser Tyr Gly Met Val Leu Tyr 1505 1510 1515 1520 Glu Leu Leu Ser Gly Gln Arg Pro Ala Leu Gly His His Gln Leu Gln 1525 1530 1535 Ile Ala Lys Lys Leu Ser Lys Gly Ile Arg Pro Val Leu Gly Gln Pro 1540 1545 1550 Glu Glu Val Gln Phe Arg Arg Leu Gln Ala Leu Met Met Glu Cys Trp 1555 1560 1565 Asp Thr Lys Pro Glu Lys Arg Pro Leu Ala Leu Ser Val Val Ser Gln 1570 1575 1580 Met Lys Asp Pro Thr Phe Ala Thr Phe Met Tyr Glu Leu Cys Cys Gly 1585 1590 1595 1600 Lys Gln Thr Ala Phe Phe Ser Ser Gln Gly Gln Glu Tyr Thr Val Val 1605 1610 1615 Phe Trp Asp Gly Lys Glu Glu Ser Arg Asn Tyr Thr Val Val Asn Thr 1620 1625 1630 Glu Lys Gly Leu Met Glu Val Gln Arg Met Cys Cys Pro Gly Met Lys 1635 1640 1645 Val Ser Cys Gln Leu Gln Val Gln Arg Ser Leu Trp Thr Ala Thr Glu 1650 1655 1660 Asn Ser Tyr Leu Val Leu Ala Gly Leu Ala Asp Gly Leu Val Ala Val 1665 1670 1675 1680 Phe Pro Val Val Arg Gly Thr Pro Lys Asp Ser Cys Ser Tyr Leu Cys 1685 1690 1695 Ser His Thr Ala Asn Arg Ser Lys Phe Ser Ile Ala Asp Glu Asp Ala 1700 1705 1710 Arg Gln Asn Pro Tyr Pro Val Lys Ala Met Glu Val Val Asn Ser Gly 1715 1720 1725 Ser Glu Val Trp Tyr Ser Asn Gly Pro Gly Leu Leu Val Ile Asp Cys 1730 1735 1740 Ala Ser Leu Glu Ile Cys Arg Arg Leu Glu Pro Tyr Met Ala Pro Ser 1745 1750 1755 1760 Met Val Thr Ser Val Val Cys Ser Ser Glu Gly Arg Gly Glu Glu Val 1765 1770 1775 Val Trp Cys Leu Asp Asp Lys Ala Asn Ser Leu Val Met Tyr His Ser 1780 1785 1790 Thr Thr Tyr Gln Leu Cys Ala Arg Tyr Phe Cys Gly Val Pro Ser Pro 1795 1800 1805 Leu Arg Asp Met Phe Pro Val Arg Pro Leu Asp Thr Glu Pro Pro Ala 1810 1815 1820 Ala Ser His Thr Ala Asn Pro Lys Val Pro Glu Gly Asp Ser Ile Ala 1825 1830 1835 1840 Asp Val Ser Ile Met Tyr Ser Glu Glu Leu Gly Thr Gln Ile Leu Ile 1845 1850 1855 His Gln Glu Ser Leu Thr Asp Tyr Cys Ser Met Ser Ser Tyr Ser Ser 1860 1865 1870 Ser Pro Pro Arg Gln Ala Ala Arg Ser Pro Ser Ser Leu Pro Ser Ser 1875 1880 1885 Pro Ala Ser Ser Ser Ser Val Pro Phe Ser Thr Asp Cys Glu Asp Ser 1890 1895 1900 Asp Met Leu His Thr Pro Gly Ala Ala Ser Asp Arg Ser Glu His Asp 1905 1910 1915 1920 Leu Thr Pro Met Asp Gly Glu Thr Phe Ser Gln His Leu Gln Ala Val 1925 1930 1935 Lys Ile Leu Ala Val Arg Asp Leu Ile Trp Val Pro Arg Arg Gly Gly 1940 1945 1950 Asp Val Ile Val Ile Gly Leu Glu Lys Asp Ser Gly Ala Gln Arg Gly 1955 1960 1965 Arg Val Ile Ala Val Leu Lys Ala Arg Glu Leu Thr Pro His Gly Val 1970 1975 1980 Leu Val Asp Ala Ala Val Val Ala Lys Asp Thr Val Val Cys Thr Phe 1985 1990 1995 2000 Glu Asn Glu Asn Thr Glu Trp Cys Leu Ala Val Trp Arg Gly Trp Gly 2005 2010 2015 Ala Arg Glu Phe Asp Ile Phe Tyr Gln Ser Tyr Glu Glu Leu Gly Arg 2020 2025 2030 Leu Glu Ala Cys Thr Arg Lys Arg 2035 2040 5 7015 DNA Homo sapiens 5 cgaggggacg cctcgcgacg gttcctggga gagctggcgg cggccttgct ctgcgcgctc 60 ttcgcgccgc cctccccgcc cgcccgcctc aggattgagg aagtgcgtct gggcccggcc 120 ccggcgcggg gggcagacgg cggtgggacg gccaggcccc ggccccgcca gtgtgtccgc 180 ccggccccgc gtcccggagg agtcagctgt gtgtccagaa cgtgccatgg agacgcttaa 240 cggtgccggg gacacgggcg gcaagccgtc cacgcggggc ggtgaccctg cagcgcggtc 300 ccgcaggacg gaaggcatcc gcgccgcgta caggcgggga gaccgcggcg gcgcccggga 360 cctgctggag gaggcctgcg accagtgcgc gtcccagctg gaaaagggcc agcttctgag 420 catcccggca gcctatgggg atctggagat ggtccgctac ctactcagca agagactggt 480 ggagctgccc accgagccca cggatgacaa cccagccgtg gtggcagcgt attttggaca 540 cacggcagtt gtgcaggaat tgcttgagtc cttaccaggt ccctgcagtc cccagcggct 600 tctgaactgg atgctggcct tggcttgcca gcgagggcac ctgggggttg tgaagctcct 660 ggtcctgacg cacggggctg acccggagag ctacgctgtc aggaagaatg agttccctgt 720 catcgtgcgc ttgcccctgt atgcggccat caagtcaggg aatgaagaca ttgcaatatt 780 cctgcttcgg catggggcct atttctgttc ctacatcttg ctggatagtc ctgaccccag 840 caaacatctg ctgagaaagt acttcattga agccagtccc ttgcccagca gttatccggg 900 aaaaacagct ctccgtgtga aatggtccca tctcagactg ccctgggtag acctagactg 960 gctcatagac atctcctgcc agatcacgga gctcgacctt tctgccaact gcctggcgac 1020 cctcccctcg gttatcccct ggggcctcat caatctccgg aagctgaacc tctccgacaa 1080 ccacctgggg gagctgcctg gcgtgcagtc atcggacgaa atcatctgtt ccaggctact 1140 tgaaattgac atttccagca acaagttgtc ccacctccct cctggattct tgcacctctc 1200 aaaacttcaa aaactgacag cttcaaaaaa ttgtttagaa aaattgttcg aagaagaaaa 1260 tgccactaac tggataggtt tacggaagct acaggaactt gatatatctg acaataaatt 1320 gacagaactc cctgccctgt tccttcactc tttcaagtcc ctcaattctc tgaatgtctc 1380 cagaaacaac ctgaaggtgt ttccagatcc ctgggcctgc cctttgaaat gttgtaaagc 1440 ttccagaaat gccctggaat gtctgccaga caaaatggct gtcttttgga aaaatcacct 1500 gaaggatgtg gatttctcag aaaacgcact caaagaagtt cccctgggac ttttccagct 1560 tgatgccctc atgttcttga ggttacaggg gaaccagctg gcggcacttc cacctcaaga 1620 gaagtggacc tgcaggcagc tcaaaaccct ggatctctcc agaaaccaac ttggcaaaaa 1680 tgaagatgga ctgaaaacga agcgtattgc ctttttcacc accagaggtc gccagcgctc 1740 cgggactgag gcagagacaa ctatggagtt cagtgcatct ctggtaacca ttgtgttcct 1800 gtctaacaac tgtaacctct gtgcatacac atgtgcagca agtgtgctgg aatttccggc 1860 cttcctaagt gagtctttgg aagtcctttg cctgaacgac aaccacctcg acacagtccc 1920 tccctcggtt tgcctactga agagcttatc agagctctac ttgggaaaca accctggcct 1980 ccgggagctc cctcctgagc tggggcagct gggcaacctc tggcagctgg acactgaaga 2040 cctgaccatc agcaatgtgc ctgcagaaat ccaaaaagaa ggccccaaag caatgctgtc 2100 ttacctgcgt gctcagctgc ggaaagcgga aaagtgcaag ctgatgaaga tgatcatcgt 2160 gggtcccccg cgccagggca agtccaccct cctggagatc ttacagacgg ggagggcccc 2220 ccaggtggtg catggagagg ccaccatcag gaccaccaag tgggagctcc agaggccggc 2280 tggctcgaga gccaaggtca aggatggtct gcgtgcagag tccctgtggg ttgagtccgt 2340 ggagttcaac gtctgggaca tcgggggacc ggccagcatg gccactgtca accagtgctt 2400 cttcacggac aaggccctgt acgtggtggt ctggaacctg gcgctggggg aggaggccgt 2460 ggccaacctc cagttctggc tgctcaacat cgaggccaag gccccaaacg ccgtggtgct 2520 ggtggtcggg acgcacctgg atttaattga agccaagttc cgtgtggaaa ggattgcaac 2580 gctgcgtgcc tatgtgctgg cactctgccg ctccccctcc ggctccaggg ccacaggctt 2640 cccagacatc accttcaaac acttacatga gatttcctgc aagagcctgg aaggtcagga 2700 agggctgcga cagctgattt tccacgtcac gtgcagcatg aaggacgtcg gcagcaccat 2760 cggctgccag cgactggcag ggcggctgat ccccaggagc tacctgagcc tgcaggaggc 2820 cgtgctggca gagcagcagc gccgcagccg ggacgacgac gtgcagtacc tgacggacag 2880 gcagctggag cagctggtgg agcagacgcc cgacaacgac atcaaggact acgaggacct 2940 gcagtcagcc atcagcttcc tcatagaaac cggcaccctg ctccatttcc cggacaccag 3000 ccacggcctg aggaacctct acttcctcga ccctatttgg ctctccgaat gtctgcagag 3060 gatctttaat attaagggct ctcggtcagt ggccaagaat ggggtgatca gagcagaaga 3120 cctcaggatg ctgctggtgg ggactggctt cacgcagcag acggaagagc agtacttcca 3180 gttcctggcc aagtttgaga tcgccctgcc cgtcgccaat gacagctacc tcctgcccca 3240 tctccttcca tctaaacctg gcctggacac ccacggtatg cggcacccca cagccaacac 3300 cattcagagg gtatttaaga tgagcttcgt tcccgttggc ttctggcaaa ggtttatagc 3360 acggatgctg atcagcctgg cggagatgga cctgcagctt tttgaaaaca agaagaatac 3420 taaaagcagg aacaggaaag tcaccattta cagttttaca ggaaaccaga gaaatcgctg 3480 tagcacattc agagtgaaaa gaaatcagac catctattgg caggaagggc tcctggtcac 3540 ttttgatggg ggctacctca gtgtggaatc ttccgacgtg aactggaaaa agaagaaaag 3600 cggaggaatg aaaattgttt gccaatcaga agtgagggac ttctcagcca tggctttcat 3660 cacggaccac gtcaattcct tgattgatca gtggtttccc gccctgacag ccacagagag 3720 cgacgggacg ccactcatgg agcagtacgt gccctgcccg gtctgcgaga cagcctgggc 3780 ccagcacacg gaccccagtg agaaatcaga ggatgtgcag tacttcgaca tggaagactg 3840 tgtcctgacg gccatcgagc gggacttcat ctcctgcccc agacacccgg acctccccgt 3900 gccgctgcag gagctggtcc ctgaactgtt catgaccgac ttcccggcca ggctcttcct 3960 ggagaacagc aagctggagc acagcgagga cgagggcagc gtcctgggcc agggcggcag 4020 tggcaccgtc atctaccggg cccggtacca gggccagcct gtggccgtca agcgcttcca 4080 catcaaaaaa ttcaagaact ttgctaacgt accggcagac accatgctga ggcacctgcg 4140 ggccaccgat gccatgaaga acttctccga gttccggcag gaggccagca tgctgcacgc 4200 gctgcagcac ccctgcatcg tggcgctcat cggcatcagc atccacccgc tctgcttcgc 4260 cctggagctc gcgccgctca gcagcctcaa caccgtgctg tccgagaacg ccagagattc 4320 ttcctttata cccctgggac acatgctcac ccaaaaaata gcctaccaga tcgcctcggg 4380 cctggcctac ctgcacaaga aaaacatcat cttctgtgac ctgaagtcgg acaacattct 4440 ggtgtggtcc cttgacgtca aggagcacat caacatcaag ctatctgact acgggatttc 4500 gaggcagtca ttccatgagg gcgccctagg cgtggagggc actcctggct accaggcccc 4560 agagatcagg cctcgcattg tatatgatga gaaggtagat atgttctcct atggaatggt 4620 gctctacgag ttgctgtcag gacagcgccc tgcactgggc caccaccagc tccagattgc 4680 caagaagctg tccaagggca tccgcccggt tctggggcag ccggaggaag tgcagttccg 4740 gcgactgcag gcgctcatga tggagtgctg ggacactaag ccagagaagc gaccgctggc 4800 cctgtcggtg gtgagccaga tgaaggaccc gacttttgcc accttcatgt atgaactgtg 4860 ctgtgggaag cagacagcct tcttctcatc ccagggccag gagtacaccg tggtgttttg 4920 ggatggaaaa gaggagtcca ggaactacac ggtggtgaac acagagaagg gcctcatgga 4980 ggtgcagagg atgtgctgcc ctgggatgaa ggtgagctgc cagctccagg tccagagatc 5040 cctgtggaca gccaccgaga attcctacct ggtcttagcg ggcctcgccg atgggcttgt 5100 ggctgtgttt cccgtggtgc ggggcacccc aaaggacagc tgctcctacc tgtgctcaca 5160 cacagccaac aggtccaagt tcagcatcgc ggatgaagac gcacggcaga acccctaccc 5220 agtgaaggcc atggaggtgg tcaacagcgg ctctgaggtc tggtacagca atgggccggg 5280 cctccttgtc atcgactgtg cctccctgga gatctgcagg cggctggagc cctacatggc 5340 cccctccatg gttacgtcag tcgtgtgcag ctctgagggc agaggggagg aggtcgtctg 5400 gtgcctggat gacaaggcca actccttggt gatgtaccac tccaccacct accagctgtg 5460 tgcccggtac ttctgcgggg tccccagccc cctcagggac atgtttcccg tgcggccctt 5520 ggacacggaa cccccggcag ccagccacac ggccaaccca aaggtgcctg agggggactc 5580 catcgcggac gtgagcatca tgtacagtga ggagctgggc acgcagatcc tgatccacca 5640 ggaatcactc actgactact gctccatgtc ctcctactcc tcatccccac cccgccaggc 5700 tgccaggtcc ccctcaagcc tccccagctc cccagcaagt tcttccagtg tgcctttctc 5760 caccgactgc gaggactcag acatgctaca tacgcccggt gctgcctccg acaggtctga 5820 gcatgacctg acccccatgg acggggagac cttcagccag cacctgcagg ccgtgaagat 5880 cctcgccgtc agagacctca tttgggtccc caggcgcggt ggagatgtta tcgtcattgg 5940 cctggagaag gattctggcg cccagcgggg ccgagtcatt gccgtcttaa aagcccgaga 6000 gctgactccg catggggtgc tggtggatgc tgccgtggtg gcaaaggaca ctgttgtgtg 6060 cacctttgaa aatgaaaaca cagagtggtg cctggccgtc tggaggggct ggggcgccag 6120 ggagttcgac attttctacc agtcctacga ggagctgggc cggctggagg cttgcactcg 6180 caagagaagg taattcctgt ggaatgactg tcacacatca gagctggctg gcccggggct 6240 gcagcctgac tcctctgcca tcggcctcta gttctccaag gacctagaag acagatggag 6300 ttctcccctg aactccttgc tgctaagaag tgctgagaag ttactcgcct ggcggtggct 6360 ccagggttct ctggttctct ggagcagagt tctctgaata ccccatcccc caactgctga 6420 ttttacagcc ccagggaaga cagtggtatc aggctgggag cggcctcctc tggcctcccc 6480 catcagtttg caggagcagg ggtgcaggat cctgttctga gctgggtcaa acaaagcagg 6540 gccgggcctt cctgccatcc ccaggtctca gatggaatta cactagaggc cctccgctgg 6600 gaagcacttg aggtagggca ggaggggggc tgtgacccct gccctttccc cgccagagac 6660 ctcaggctct cagcacattc cacaggctcc tgagtccccg aggcctgggc cagcttgggc 6720 aagccaagat cagatgtctc tgtgttcggg aaggtctccg tgtgggaaag cccttggggg 6780 atcccgggtg aggagtgttg ccccatccag agaatgaatg agttccttta agtgccaccg 6840 ccagcaagcc cagaggcaca cattctgagt gcacccgctt agcctttaca ttcctctcca 6900 ccgacaaaag gaaggggaaa ctcaatcagc aggacttcag aaagggcctt gtgtttatag 6960 ctttgtcaag taaatttgga cgcagctgga aacacaggcc tgtttgttgc acata 7015 6 1987 PRT Homo sapiens 6 Met Glu Thr Leu Asn Gly Ala Gly Asp Thr Gly Gly Lys Pro Ser Thr 1 5 10 15 Arg Gly Gly Asp Pro Ala Ala Arg Ser Arg Arg Thr Glu Gly Ile Arg 20 25 30 Ala Ala Tyr Arg Arg Gly Asp Arg Gly Gly Ala Arg Asp Leu Leu Glu 35 40 45 Glu Ala Cys Asp Gln Cys Ala Ser Gln Leu Glu Lys Gly Gln Leu Leu 50 55 60 Ser Ile Pro Ala Ala Tyr Gly Asp Leu Glu Met Val Arg Tyr Leu Leu 65 70 75 80 Ser Lys Arg Leu Val Glu Leu Pro Thr Glu Pro Thr Asp Asp Asn Pro 85 90 95 Ala Val Val Ala Ala Tyr Phe Gly His Thr Ala Val Val Gln Glu Leu 100 105 110 Leu Glu Ser Leu Pro Gly Pro Cys Ser Pro Gln Arg Leu Leu Asn Trp 115 120 125 Met Leu Ala Leu Ala Cys Gln Arg Gly His Leu Gly Val Val Lys Leu 130 135 140 Leu Val Leu Thr His Gly Ala Asp Pro Glu Ser Tyr Ala Val Arg Lys 145 150 155 160 Asn Glu Phe Pro Val Ile Val Arg Leu Pro Leu Tyr Ala Ala Ile Lys 165 170 175 Ser Gly Asn Glu Asp Ile Ala Ile Phe Leu Leu Arg His Gly Ala Tyr 180 185 190 Phe Cys Ser Tyr Ile Leu Leu Asp Ser Pro Asp Pro Ser Lys His Leu 195 200 205 Leu Arg Lys Tyr Phe Ile Glu Ala Ser Pro Leu Pro Ser Ser Tyr Pro 210 215 220 Gly Lys Thr Ala Leu Arg Val Lys Trp Ser His Leu Arg Leu Pro Trp 225 230 235 240 Val Asp Leu Asp Trp Leu Ile Asp Ile Ser Cys Gln Ile Thr Glu Leu 245 250 255 Asp Leu Ser Ala Asn Cys Leu Ala Thr Leu Pro Ser Val Ile Pro Trp 260 265 270 Gly Leu Ile Asn Leu Arg Lys Leu Asn Leu Ser Asp Asn His Leu Gly 275 280 285 Glu Leu Pro Gly Val Gln Ser Ser Asp Glu Ile Ile Cys Ser Arg Leu 290 295 300 Leu Glu Ile Asp Ile Ser Ser Asn Lys Leu Ser His Leu Pro Pro Gly 305 310 315 320 Phe Leu His Leu Ser Lys Leu Gln Lys Leu Thr Ala Ser Lys Asn Cys 325 330 335 Leu Glu Lys Leu Phe Glu Glu Glu Asn Ala Thr Asn Trp Ile Gly Leu 340 345 350 Arg Lys Leu Gln Glu Leu Asp Ile Ser Asp Asn Lys Leu Thr Glu Leu 355 360 365 Pro Ala Leu Phe Leu His Ser Phe Lys Ser Leu Asn Ser Leu Asn Val 370 375 380 Ser Arg Asn Asn Leu Lys Val Phe Pro Asp Pro Trp Ala Cys Pro Leu 385 390 395 400 Lys Cys Cys Lys Ala Ser Arg Asn Ala Leu Glu Cys Leu Pro Asp Lys 405 410 415 Met Ala Val Phe Trp Lys Asn His Leu Lys Asp Val Asp Phe Ser Glu 420 425 430 Asn Ala Leu Lys Glu Val Pro Leu Gly Leu Phe Gln Leu Asp Ala Leu 435 440 445 Met Phe Leu Arg Leu Gln Gly Asn Gln Leu Ala Ala Leu Pro Pro Gln 450 455 460 Glu Lys Trp Thr Cys Arg Gln Leu Lys Thr Leu Asp Leu Ser Arg Asn 465 470 475 480 Gln Leu Gly Lys Asn Glu Asp Gly Leu Lys Thr Lys Arg Ile Ala Phe 485 490 495 Phe Thr Thr Arg Gly Arg Gln Arg Ser Gly Thr Glu Ala Glu Thr Thr 500 505 510 Met Glu Phe Ser Ala Ser Leu Val Thr Ile Val Phe Leu Ser Asn Asn 515 520 525 Cys Asn Leu Cys Ala Tyr Thr Cys Ala Ala Ser Val Leu Glu Phe Pro 530 535 540 Ala Phe Leu Ser Glu Ser Leu Glu Val Leu Cys Leu Asn Asp Asn His 545 550 555 560 Leu Asp Thr Val Pro Pro Ser Val Cys Leu Leu Lys Ser Leu Ser Glu 565 570 575 Leu Tyr Leu Gly Asn Asn Pro Gly Leu Arg Glu Leu Pro Pro Glu Leu 580 585 590 Gly Gln Leu Gly Asn Leu Trp Gln Leu Asp Thr Glu Asp Leu Thr Ile 595 600 605 Ser Asn Val Pro Ala Glu Ile Gln Lys Glu Gly Pro Lys Ala Met Leu 610 615 620 Ser Tyr Leu Arg Ala Gln Leu Arg Lys Ala Glu Lys Cys Lys Leu Met 625 630 635 640 Lys Met Ile Ile Val Gly Pro Pro Arg Gln Gly Lys Ser Thr Leu Leu 645 650 655 Glu Ile Leu Gln Thr Gly Arg Ala Pro Gln Val Val His Gly Glu Ala 660 665 670 Thr Ile Arg Thr Thr Lys Trp Glu Leu Gln Arg Pro Ala Gly Ser Arg 675 680 685 Ala Lys Val Lys Asp Gly Leu Arg Ala Glu Ser Leu Trp Val Glu Ser 690 695 700 Val Glu Phe Asn Val Trp Asp Ile Gly Gly Pro Ala Ser Met Ala Thr 705 710 715 720 Val Asn Gln Cys Phe Phe Thr Asp Lys Ala Leu Tyr Val Val Val Trp 725 730 735 Asn Leu Ala Leu Gly Glu Glu Ala Val Ala Asn Leu Gln Phe Trp Leu 740 745 750 Leu Asn Ile Glu Ala Lys Ala Pro Asn Ala Val Val Leu Val Val Gly 755 760 765 Thr His Leu Asp Leu Ile Glu Ala Lys Phe Arg Val Glu Arg Ile Ala 770 775 780 Thr Leu Arg Ala Tyr Val Leu Ala Leu Cys Arg Ser Pro Ser Gly Ser 785 790 795 800 Arg Ala Thr Gly Phe Pro Asp Ile Thr Phe Lys His Leu His Glu Ile 805 810 815 Ser Cys Lys Ser Leu Glu Gly Gln Glu Gly Leu Arg Gln Leu Ile Phe 820 825 830 His Val Thr Cys Ser Met Lys Asp Val Gly Ser Thr Ile Gly Cys Gln 835 840 845 Arg Leu Ala Gly Arg Leu Ile Pro Arg Ser Tyr Leu Ser Leu Gln Glu 850 855 860 Ala Val Leu Ala Glu Gln Gln Arg Arg Ser Arg Asp Asp Asp Val Gln 865 870 875 880 Tyr Leu Thr Asp Arg Gln Leu Glu Gln Leu Val Glu Gln Thr Pro Asp 885 890 895 Asn Asp Ile Lys Asp Tyr Glu Asp Leu Gln Ser Ala Ile Ser Phe Leu 900 905 910 Ile Glu Thr Gly Thr Leu Leu His Phe Pro Asp Thr Ser His Gly Leu 915 920 925 Arg Asn Leu Tyr Phe Leu Asp Pro Ile Trp Leu Ser Glu Cys Leu Gln 930 935 940 Arg Ile Phe Asn Ile Lys Gly Ser Arg Ser Val Ala Lys Asn Gly Val 945 950 955 960 Ile Arg Ala Glu Asp Leu Arg Met Leu Leu Val Gly Thr Gly Phe Thr 965 970 975 Gln Gln Thr Glu Glu Gln Tyr Phe Gln Phe Leu Ala Lys Phe Glu Ile 980 985 990 Ala Leu Pro Val Ala Asn Asp Ser Tyr Leu Leu Pro His Leu Leu Pro 995 1000 1005 Ser Lys Pro Gly Leu Asp Thr His Gly Met Arg His Pro Thr Ala Asn 1010 1015 1020 Thr Ile Gln Arg Val Phe Lys Met Ser Phe Val Pro Val Gly Phe Trp 1025 1030 1035 1040 Gln Arg Phe Ile Ala Arg Met Leu Ile Ser Leu Ala Glu Met Asp Leu 1045 1050 1055 Gln Leu Phe Glu Asn Lys Lys Asn Thr Lys Ser Arg Asn Arg Lys Val 1060 1065 1070 Thr Ile Tyr Ser Phe Thr Gly Asn Gln Arg Asn Arg Cys Ser Thr Phe 1075 1080 1085 Arg Val Lys Arg Asn Gln Thr Ile Tyr Trp Gln Glu Gly Leu Leu Val 1090 1095 1100 Thr Phe Asp Gly Gly Tyr Leu Ser Val Glu Ser Ser Asp Val Asn Trp 1105 1110 1115 1120 Lys Lys Lys Lys Ser Gly Gly Met Lys Ile Val Cys Gln Ser Glu Val 1125 1130 1135 Arg Asp Phe Ser Ala Met Ala Phe Ile Thr Asp His Val Asn Ser Leu 1140 1145 1150 Ile Asp Gln Trp Phe Pro Ala Leu Thr Ala Thr Glu Ser Asp Gly Thr 1155 1160 1165 Pro Leu Met Glu Gln Tyr Val Pro Cys Pro Val Cys Glu Thr Ala Trp 1170 1175 1180 Ala Gln His Thr Asp Pro Ser Glu Lys Ser Glu Asp Val Gln Tyr Phe 1185 1190 1195 1200 Asp Met Glu Asp Cys Val Leu Thr Ala Ile Glu Arg Asp Phe Ile Ser 1205 1210 1215 Cys Pro Arg His Pro Asp Leu Pro Val Pro Leu Gln Glu Leu Val Pro 1220 1225 1230 Glu Leu Phe Met Thr Asp Phe Pro Ala Arg Leu Phe Leu Glu Asn Ser 1235 1240 1245 Lys Leu Glu His Ser Glu Asp Glu Gly Ser Val Leu Gly Gln Gly Gly 1250 1255 1260 Ser Gly Thr Val Ile Tyr Arg Ala Arg Tyr Gln Gly Gln Pro Val Ala 1265 1270 1275 1280 Val Lys Arg Phe His Ile Lys Lys Phe Lys Asn Phe Ala Asn Val Pro 1285 1290 1295 Ala Asp Thr Met Leu Arg His Leu Arg Ala Thr Asp Ala Met Lys Asn 1300 1305 1310 Phe Ser Glu Phe Arg Gln Glu Ala Ser Met Leu His Ala Leu Gln His 1315 1320 1325 Pro Cys Ile Val Ala Leu Ile Gly Ile Ser Ile His Pro Leu Cys Phe 1330 1335 1340 Ala Leu Glu Leu Ala Pro Leu Ser Ser Leu Asn Thr Val Leu Ser Glu 1345 1350 1355 1360 Asn Ala Arg Asp Ser Ser Phe Ile Pro Leu Gly His Met Leu Thr Gln 1365 1370 1375 Lys Ile Ala Tyr Gln Ile Ala Ser Gly Leu Ala Tyr Leu His Lys Lys 1380 1385 1390 Asn Ile Ile Phe Cys Asp Leu Lys Ser Asp Asn Ile Leu Val Trp Ser 1395 1400 1405 Leu Asp Val Lys Glu His Ile Asn Ile Lys Leu Ser Asp Tyr Gly Ile 1410 1415 1420 Ser Arg Gln Ser Phe His Glu Gly Ala Leu Gly Val Glu Gly Thr Pro 1425 1430 1435 1440 Gly Tyr Gln Ala Pro Glu Ile Arg Pro Arg Ile Val Tyr Asp Glu Lys 1445 1450 1455 Val Asp Met Phe Ser Tyr Gly Met Val Leu Tyr Glu Leu Leu Ser Gly 1460 1465 1470 Gln Arg Pro Ala Leu Gly His His Gln Leu Gln Ile Ala Lys Lys Leu 1475 1480 1485 Ser Lys Gly Ile Arg Pro Val Leu Gly Gln Pro Glu Glu Val Gln Phe 1490 1495 1500 Arg Arg Leu Gln Ala Leu Met Met Glu Cys Trp Asp Thr Lys Pro Glu 1505 1510 1515 1520 Lys Arg Pro Leu Ala Leu Ser Val Val Ser Gln Met Lys Asp Pro Thr 1525 1530 1535 Phe Ala Thr Phe Met Tyr Glu Leu Cys Cys Gly Lys Gln Thr Ala Phe 1540 1545 1550 Phe Ser Ser Gln Gly Gln Glu Tyr Thr Val Val Phe Trp Asp Gly Lys 1555 1560 1565 Glu Glu Ser Arg Asn Tyr Thr Val Val Asn Thr Glu Lys Gly Leu Met 1570 1575 1580 Glu Val Gln Arg Met Cys Cys Pro Gly Met Lys Val Ser Cys Gln Leu 1585 1590 1595 1600 Gln Val Gln Arg Ser Leu Trp Thr Ala Thr Glu Asn Ser Tyr Leu Val 1605 1610 1615 Leu Ala Gly Leu Ala Asp Gly Leu Val Ala Val Phe Pro Val Val Arg 1620 1625 1630 Gly Thr Pro Lys Asp Ser Cys Ser Tyr Leu Cys Ser His Thr Ala Asn 1635 1640 1645 Arg Ser Lys Phe Ser Ile Ala Asp Glu Asp Ala Arg Gln Asn Pro Tyr 1650 1655 1660 Pro Val Lys Ala Met Glu Val Val Asn Ser Gly Ser Glu Val Trp Tyr 1665 1670 1675 1680 Ser Asn Gly Pro Gly Leu Leu Val Ile Asp Cys Ala Ser Leu Glu Ile 1685 1690 1695 Cys Arg Arg Leu Glu Pro Tyr Met Ala Pro Ser Met Val Thr Ser Val 1700 1705 1710 Val Cys Ser Ser Glu Gly Arg Gly Glu Glu Val Val Trp Cys Leu Asp 1715 1720 1725 Asp Lys Ala Asn Ser Leu Val Met Tyr His Ser Thr Thr Tyr Gln Leu 1730 1735 1740 Cys Ala Arg Tyr Phe Cys Gly Val Pro Ser Pro Leu Arg Asp Met Phe 1745 1750 1755 1760 Pro Val Arg Pro Leu Asp Thr Glu Pro Pro Ala Ala Ser His Thr Ala 1765 1770 1775 Asn Pro Lys Val Pro Glu Gly Asp Ser Ile Ala Asp Val Ser Ile Met 1780 1785 1790 Tyr Ser Glu Glu Leu Gly Thr Gln Ile Leu Ile His Gln Glu Ser Leu 1795 1800 1805 Thr Asp Tyr Cys Ser Met Ser Ser Tyr Ser Ser Ser Pro Pro Arg Gln 1810 1815 1820 Ala Ala Arg Ser Pro Ser Ser Leu Pro Ser Ser Pro Ala Ser Ser Ser 1825 1830 1835 1840 Ser Val Pro Phe Ser Thr Asp Cys Glu Asp Ser Asp Met Leu His Thr 1845 1850 1855 Pro Gly Ala Ala Ser Asp Arg Ser Glu His Asp Leu Thr Pro Met Asp 1860 1865 1870 Gly Glu Thr Phe Ser Gln His Leu Gln Ala Val Lys Ile Leu Ala Val 1875 1880 1885 Arg Asp Leu Ile Trp Val Pro Arg Arg Gly Gly Asp Val Ile Val Ile 1890 1895 1900 Gly Leu Glu Lys Asp Ser Gly Ala Gln Arg Gly Arg Val Ile Ala Val 1905 1910 1915 1920 Leu Lys Ala Arg Glu Leu Thr Pro His Gly Val Leu Val Asp Ala Ala 1925 1930 1935 Val Val Ala Lys Asp Thr Val Val Cys Thr Phe Glu Asn Glu Asn Thr 1940 1945 1950 Glu Trp Cys Leu Ala Val Trp Arg Gly Trp Gly Ala Arg Glu Phe Asp 1955 1960 1965 Ile Phe Tyr Gln Ser Tyr Glu Glu Leu Gly Arg Leu Glu Ala Cys Thr 1970 1975 1980 Arg Lys Arg 1985 7 7229 DNA Homo sapiens 7 gcggccgccg aggggacgcc tcgtgacggt tcctgggaga gctggcggcg gccttgctct 60 gcgcgctctt cgcgccgccc tccccgcccg cccgcctcag gattgaggaa gtgcgtctgg 120 gcccggcccc ggcgcggggg gcagacggcg gtgggacggc caggccccgg ccccgccagt 180 gtgtccgccc ggccccgcgt cccggagcgc ccgcacccgg ccccgccgcc gcctcagagc 240 aagaaagctt tctgctcagc catggctacg agtccacgcc ttaatgcacc ccacagccag 300 cggcagtggc agtgacaaca gcgggacctg cctttgaaga tcggctgctg caagggttga 360 tggctggcat gtcgcaaaga ccccccagca tgtactggtg tgtggggccg gaggagtcag 420 ctgtgtgtcc agaacgtgcc atggagacgc ttaacggtgc cggggacacg ggcggcaagc 480 cgtccacgcg gggcggtgac cctgcagcgc ggtcccgcag gacggaaggc atccgcgccg 540 cgtacaggcg gggagaccgc ggcggcgccc gggacctgct ggaggaggcc tgcgaccagt 600 gcgcgtccca gctggaaaag ggccagcttc tgagcatccc ggcagcctat ggggatctgg 660 agatggtccg ctacctactc agcaagagac tggtggagct gcccaccgag cccacggatg 720 acaacccagc cgtggtggca gcgtattttg gacacacggc agttgtgcag gaattgcttg 780 agtccttacc aggtccctgc agtccccagc ggcttctgaa ctggatgctg gccttggctt 840 gccagcgagg gcacctgggg gttgtgaagc tcctggtcct gacgcacggg gctgacccgg 900 agagctacgc tgtcaggaag aatgagttcc ctgtcatcgt gcgcttgccc ctgtatgcgg 960 ccatcaagtc agggaatgaa gacattgcaa tattcctgct tcggcatggg gcctatttct 1020 gttcctacat cttgctggat agtcctgacc ccagcaaaca tctgctgaga aagtacttca 1080 ttgaagccag tcccttgccc agcagttatc cgggaaaaac agctctccgt gtgaaatggt 1140 cccatctcag actgccctgg gtagacctag actggctcat agacatctcc tgccagatca 1200 cggagctcga cctttctgcc aactgcctgg cgaccctccc ctcggttatc ccctggggcc 1260 tcatcaatct ccggaagctg aacctctccg acaaccacct gggggagctg cctggcgtgc 1320 agtcatcgga cgaaatcatc tgttccaggc tacttgaaat tgacatttcc agcaacaagt 1380 tgtcccacct ccctcctgga ttcttgcacc tctcaaaact tcaaaaactg acagcttcaa 1440 aaaattgttt agaaaaattg ttcgaagaag aaaatgccac taactggata ggtttacgga 1500 agctacagga acttgatata tctgacaata aattgacaga actccctgcc ctgttccttc 1560 actctttcaa gtccctcaat tctctgaatg tctccagaaa caacctgaag gtgtttccag 1620 atccctgggc ctgccctttg aaatgttgta aagcttccag aaatgccctg gaatgtctgc 1680 cagacaaaat ggctgtcttt tggaaaaatc acctgaagga tgtggatttc tcagaaaacg 1740 cactcaaaga agttcccctg ggacttttcc agcttgatgc cctcatgttc ttgaggttac 1800 aggggaacca gctggcggca cttccacctc aagagaagtg gacctgcagg cagctcaaaa 1860 ccctggatct ctccagaaac caacttggca aaaatgaaga tggactgaaa acgaagcgta 1920 ttgccttttt caccaccaga ggtcgccagc gctccgggac tgaggcagag acaactatgg 1980 agttcagtgc atctctggta accattgtgt tcctgtctaa caactgtaac ctctgtgcat 2040 acacatgtgc agcaagtgtg ctggaatttc cggccttcct aagtgagtct ttggaagtcc 2100 tttgcctgaa cgacaaccac ctcgacacag tccctccctc ggtttgccta ctgaagagct 2160 tatcagagct ctacttggga aacaaccctg gcctccggga gctccctcct gagctggggc 2220 agctgggcaa cctctggcag ctggacactg aagacctgac catcagcaat gtgcctgcag 2280 aaatccaaaa agaaggcccc aaagcaatgc tgtcttacct gcgtgctcag ctgcggaaag 2340 cggaaaagtg caagctgatg aagatgatca tcgtgggtcc cccgcgccag ggcaagtcca 2400 ccctcctgga gatcttacag acggggaggg ccccccaggt ggtgcatgga gaggccacca 2460 tcaggaccac caagtgggag ctccagaggc cggctggctc gagagccaag gtcaaggatg 2520 gtctgcgtgc agagtccctg tgggttgagt ccgtggagtt caacgtctgg gacatcgggg 2580 gaccggccag catggccact gtcaaccagt gcttcttcac ggacaaggcc ctgtacgtgg 2640 tggtctggaa cctggcgctg ggggaggagg ccgtggccaa cctccagttc tggctgctca 2700 acatcgaggc caaggcccca aacgccgtgg tgctggtggt cgggacgcac ctggatttaa 2760 ttgaagccaa gttccgtgtg gaaaggattg caacgctgcg tgcctatgtg ctggcactct 2820 gccgctcccc ctccggctcc agggccacag gcttcccaga catcaccttc aaacacttac 2880 atgagatttc ctgcaagagc ctggaaggtc aggaagggct gcgacagctg attttccacg 2940 tcacgtgcag catgaaggac gtcggcagca ccatcggctg ccagcgactg gcagggcggc 3000 tgatccccag gagctacctg agcctgcagg aggccgtgct ggcagagcag cagcgccgca 3060 gccgggacga cgacgtgcag tacctgacgg acaggcagct ggagcagctg gtggagcaga 3120 cgcccgacaa cgacatcaag gactacgagg acctgcagtc agccatcagc ttcctcatag 3180 aaaccggcac cctgctccat ttcccggaca ccagccacgg cctgaggaac ctctacttcc 3240 tcgaccctat ttggctctcc gaatgtctgc agaggatctt taatattaag ggctctcggt 3300 cagtggccaa gaatggggtg atcagagcag aagacctcag gatgctgctg gtggggactg 3360 gcttcacgca gcagacggaa gagcagtact tccagttcct ggccaagttt gagatcgccc 3420 tgcccgtcgc caatgacagc tacctcctgc cccatctcct tccatctaaa cctggcctgg 3480 acacccacgg tatgcggcac cccacagcca acaccattca gagggtattt aagatgagct 3540 tcgttcccgt tggcttctgg caaaggttta tagcacggat gctgatcagc ctggcggaga 3600 tggacctgca gctttttgaa aacaagaaga atactaaaag caggaacagg aaagtcacca 3660 tttacagttt tacaggaaac cagagaaatc gctgtagcac attcagagtg aaaagaaatc 3720 agaccatcta ttggcaggaa gggctcctgg tcacttttga tgggggctac ctcagtgtgg 3780 aatcttccga cgtgaactgg aaaaagaaga aaagcggagg aatgaaaatt gtttgccaat 3840 cagaagtgag ggacttctca gccatggctt tcatcacgga ccacgtcaat tccttgattg 3900 atcagtggtt tcccgccctg acagccacag agagcgacgg gacgccactc atggagcagt 3960 acgtgccctg cccggtctgc gagacagcct gggcccagca cacggacccc agtgagaaat 4020 cagaggatgt gcagtacttc gacatggaag actgtgtcct gacggccatc gagcgggact 4080 tcatctcctg ccccagacac ccggacctcc ccgtgccgct gcaggagctg gtccctgaac 4140 tgttcatgac cgacttcccg gccaggctct tcctggagaa cagcaagctg gagcacagcg 4200 aggacgaggg cagcgtcctg ggccagggcg gcagtggcac cgtcatctac cgggcccggt 4260 accagggcca gcctgtggcc gtcaagcgct tccacatcaa aaaattcaag aactttgcta 4320 acgtaccggc agacaccatg ctgaggcacc tgcgggccac cgatgccatg aagaacttct 4380 ccgagttccg gcaggaggcc agcatgctgc acgcgctgca gcacccctgc atcgtggcgc 4440 tcatcggcat cagcatccac ccgctctgct tcgccctgga gctcgcgccg ctcagcagcc 4500 tcaacaccgt gctgtccgag aacgccagag attcttcctt tatacccctg ggacacatgc 4560 tcacccaaaa aatagcctac cagatcgcct cgggcctggc ctacctgcac aagaaaaaca 4620 tcatcttctg tgacctgaag tcggacaaca ttctggtgtg gtcccttgac gtcaaggagc 4680 acatcaacat caagctatct gactacggga tttcgaggca gtcattccat gagggcgccc 4740 taggcgtgga gggcactcct ggctaccagg ccccagagat caggcctcgc attgtatatg 4800 atgagaaggt agatatgttc tcctatggaa tggtgctcta cgagttgctg tcaggacagc 4860 gccctgcact gggccaccac cagctccaga ttgccaagaa gctgtccaag ggcatccgcc 4920 cggttctggg gcagccggag gaagtgcagt tccggcgact gcaggcgctc atgatggagt 4980 gctgggacac taagccagag aagcgaccgc tggccctgtc ggtggtgagc cagatgaagg 5040 acccgacttt tgccaccttc atgtatgaac tgtgctgtgg gaagcagaca gccttcttct 5100 catcccaggg ccaggagtac accgtggtgt tttgggatgg aaaagaggag tccaggaact 5160 acacggtggt gaacacagag aagggcctca tggaggtgca gaggatgtgc tgccctggga 5220 tgaaggtgag ctgccagctc caggtccaga gatccctgtg gacagccacc gagaattcct 5280 acctggtctt agcgggcctc gccgatgggc ttgtggctgt gtttcccgtg gtgcggggca 5340 ccccaaagga cagctgctcc tacctgtgct cacacacagc caacaggtcc aagttcagca 5400 tcgcggatga agacgcacgg cagaacccct acccagtgaa ggccatggag gtggtcaaca 5460 gcggctctga ggtctggtac agcaatgggc cgggcctcct tgtcatcgac tgtgcctccc 5520 tggagatctg caggcggctg gagccctaca tggccccctc catggttacg tcagtcgtgt 5580 gcagctctga gggcagaggg gaggaggtcg tctggtgcct ggatgacaag gccaactcct 5640 tggtgatgta ccactccacc acctaccagc tgtgtgcccg gtacttctgc ggggtcccca 5700 gccccctcag ggacatgttt cccgtgcggc ccttggacac ggaacccccg gcagccagcc 5760 acacggccaa cccaaaggtg cctgaggggg actccatcgc ggacgtgagc atcatgtaca 5820 gtgaggagct gggcacgcag atcctgatcc accaggaatc actcactgac tactgctcca 5880 tgtcctccta ctcctcatcc ccaccccgcc aggctgccag gtccccctca agcctcccca 5940 gctccccagc aagttcttcc agtgtgcctt tctccaccga ctgcgaggac tcagacatgc 6000 tacatacgcc cggtgctgcc tccgacaggt ctgagcatga cctgaccccc atggacgggg 6060 agaccttcag ccagcacctg caggccgtga agatcctcgc cgtcagagac ctcatttggg 6120 tccccaggcg cggtggagat gttatcgtca ttggcctgga gaaggattct ggcgcccagc 6180 ggggccgagt cattgccgtc ttaaaagccc gagagctgac tccgcatggg gtgctggtgg 6240 atgctgccgt ggtggcaaag gacactgttg tgtgcacctt tgaaaatgaa aacacagagt 6300 ggtgcctggc cgtctggagg ggctggggcg ccagggagtt cgacattttc taccagtcct 6360 acgaggagct gggccggctg gaggcttgca ctcgcaagag aaggtaattc ctgtggaatg 6420 actgtcacac atcagagctg gctggcccgg ggctgcagcc tgactcctct gccatcggcc 6480 tctagttctc caaggaccta gaagacagat ggagttctcc cctgaactcc ttgctgctaa 6540 gaagtgctga gaagttactc gcctggcggt ggctccaggg ttctctggtt ctctggagca 6600 gagttctctg aataccccat cccccaactg ctgattttac agccccaggg aagacagtgg 6660 tatcaggctg ggagcggcct cctctggcct cccccatcag tttgcaggag caggggtgca 6720 ggatcctgtt ctgagctggg tcaaacaaag cagggccggg ccttcctgcc atccccaggt 6780 ctcagatgga attacactag aggccctccg ctgggaagca cttgaggtag ggcaggaggg 6840 gggctgtgac ccctgccctt tccccgccag agacctcagg ctctcagcac attccacagg 6900 ctcctgagtc cccgaggcct gggccagctt gggcaagcca agatcagatg tctctgtgtt 6960 cgggaaggtc tccgtgtggg aaagcccttg ggggatcccg ggtgaggagt gttgccccat 7020 ccagagaatg aatgagttcc tttaagtgcc accgccagca agcccagagg cacacattct 7080 gagtgcaccc gcttagcctt tacattcctc tccaccgaca aaaggaaggg gaaactcaat 7140 cagcaggact tcagaaaggg ccttgtgttt atagctttgt caagtaaatt tggacgcagc 7200 tggaaacaca ggcctgtttg ttgcacata 7229 8 2014 PRT Homo sapiens 8 Met Ala Gly Met Ser Gln Arg Pro Pro Ser Met Tyr Trp Cys Val Gly 1 5 10 15 Pro Glu Glu Ser Ala Val Cys Pro Glu Arg Ala Met Glu Thr Leu Asn 20 25 30 Gly Ala Gly Asp Thr Gly Gly Lys Pro Ser Thr Arg Gly Gly Asp Pro 35 40 45 Ala Ala Arg Ser Arg Arg Thr Glu Gly Ile Arg Ala Ala Tyr Arg Arg 50 55 60 Gly Asp Arg Gly Gly Ala Arg Asp Leu Leu Glu Glu Ala Cys Asp Gln 65 70 75 80 Cys Ala Ser Gln Leu Glu Lys Gly Gln Leu Leu Ser Ile Pro Ala Ala 85 90 95 Tyr Gly Asp Leu Glu Met Val Arg Tyr Leu Leu Ser Lys Arg Leu Val 100 105 110 Glu Leu Pro Thr Glu Pro Thr Asp Asp Asn Pro Ala Val Val Ala Ala 115 120 125 Tyr Phe Gly His Thr Ala Val Val Gln Glu Leu Leu Glu Ser Leu Pro 130 135 140 Gly Pro Cys Ser Pro Gln Arg Leu Leu Asn Trp Met Leu Ala Leu Ala 145 150 155 160 Cys Gln Arg Gly His Leu Gly Val Val Lys Leu Leu Val Leu Thr His 165 170 175 Gly Ala Asp Pro Glu Ser Tyr Ala Val Arg Lys Asn Glu Phe Pro Val 180 185 190 Ile Val Arg Leu Pro Leu Tyr Ala Ala Ile Lys Ser Gly Asn Glu Asp 195 200 205 Ile Ala Ile Phe Leu Leu Arg His Gly Ala Tyr Phe Cys Ser Tyr Ile 210 215 220 Leu Leu Asp Ser Pro Asp Pro Ser Lys His Leu Leu Arg Lys Tyr Phe 225 230 235 240 Ile Glu Ala Ser Pro Leu Pro Ser Ser Tyr Pro Gly Lys Thr Ala Leu 245 250 255 Arg Val Lys Trp Ser His Leu Arg Leu Pro Trp Val Asp Leu Asp Trp 260 265 270 Leu Ile Asp Ile Ser Cys Gln Ile Thr Glu Leu Asp Leu Ser Ala Asn 275 280 285 Cys Leu Ala Thr Leu Pro Ser Val Ile Pro Trp Gly Leu Ile Asn Leu 290 295 300 Arg Lys Leu Asn Leu Ser Asp Asn His Leu Gly Glu Leu Pro Gly Val 305 310 315 320 Gln Ser Ser Asp Glu Ile Ile Cys Ser Arg Leu Leu Glu Ile Asp Ile 325 330 335 Ser Ser Asn Lys Leu Ser His Leu Pro Pro Gly Phe Leu His Leu Ser 340 345 350 Lys Leu Gln Lys Leu Thr Ala Ser Lys Asn Cys Leu Glu Lys Leu Phe 355 360 365 Glu Glu Glu Asn Ala Thr Asn Trp Ile Gly Leu Arg Lys Leu Gln Glu 370 375 380 Leu Asp Ile Ser Asp Asn Lys Leu Thr Glu Leu Pro Ala Leu Phe Leu 385 390 395 400 His Ser Phe Lys Ser Leu Asn Ser Leu Asn Val Ser Arg Asn Asn Leu 405 410 415 Lys Val Phe Pro Asp Pro Trp Ala Cys Pro Leu Lys Cys Cys Lys Ala 420 425 430 Ser Arg Asn Ala Leu Glu Cys Leu Pro Asp Lys Met Ala Val Phe Trp 435 440 445 Lys Asn His Leu Lys Asp Val Asp Phe Ser Glu Asn Ala Leu Lys Glu 450 455 460 Val Pro Leu Gly Leu Phe Gln Leu Asp Ala Leu Met Phe Leu Arg Leu 465 470 475 480 Gln Gly Asn Gln Leu Ala Ala Leu Pro Pro Gln Glu Lys Trp Thr Cys 485 490 495 Arg Gln Leu Lys Thr Leu Asp Leu Ser Arg Asn Gln Leu Gly Lys Asn 500 505 510 Glu Asp Gly Leu Lys Thr Lys Arg Ile Ala Phe Phe Thr Thr Arg Gly 515 520 525 Arg Gln Arg Ser Gly Thr Glu Ala Glu Thr Thr Met Glu Phe Ser Ala 530 535 540 Ser Leu Val Thr Ile Val Phe Leu Ser Asn Asn Cys Asn Leu Cys Ala 545 550 555 560 Tyr Thr Cys Ala Ala Ser Val Leu Glu Phe Pro Ala Phe Leu Ser Glu 565 570 575 Ser Leu Glu Val Leu Cys Leu Asn Asp Asn His Leu Asp Thr Val Pro 580 585 590 Pro Ser Val Cys Leu Leu Lys Ser Leu Ser Glu Leu Tyr Leu Gly Asn 595 600 605 Asn Pro Gly Leu Arg Glu Leu Pro Pro Glu Leu Gly Gln Leu Gly Asn 610 615 620 Leu Trp Gln Leu Asp Thr Glu Asp Leu Thr Ile Ser Asn Val Pro Ala 625 630 635 640 Glu Ile Gln Lys Glu Gly Pro Lys Ala Met Leu Ser Tyr Leu Arg Ala 645 650 655 Gln Leu Arg Lys Ala Glu Lys Cys Lys Leu Met Lys Met Ile Ile Val 660 665 670 Gly Pro Pro Arg Gln Gly Lys Ser Thr Leu Leu Glu Ile Leu Gln Thr 675 680 685 Gly Arg Ala Pro Gln Val Val His Gly Glu Ala Thr Ile Arg Thr Thr 690 695 700 Lys Trp Glu Leu Gln Arg Pro Ala Gly Ser Arg Ala Lys Val Lys Asp 705 710 715 720 Gly Leu Arg Ala Glu Ser Leu Trp Val Glu Ser Val Glu Phe Asn Val 725 730 735 Trp Asp Ile Gly Gly Pro Ala Ser Met Ala Thr Val Asn Gln Cys Phe 740 745 750 Phe Thr Asp Lys Ala Leu Tyr Val Val Val Trp Asn Leu Ala Leu Gly 755 760 765 Glu Glu Ala Val Ala Asn Leu Gln Phe Trp Leu Leu Asn Ile Glu Ala 770 775 780 Lys Ala Pro Asn Ala Val Val Leu Val Val Gly Thr His Leu Asp Leu 785 790 795 800 Ile Glu Ala Lys Phe Arg Val Glu Arg Ile Ala Thr Leu Arg Ala Tyr 805 810 815 Val Leu Ala Leu Cys Arg Ser Pro Ser Gly Ser Arg Ala Thr Gly Phe 820 825 830 Pro Asp Ile Thr Phe Lys His Leu His Glu Ile Ser Cys Lys Ser Leu 835 840 845 Glu Gly Gln Glu Gly Leu Arg Gln Leu Ile Phe His Val Thr Cys Ser 850 855 860 Met Lys Asp Val Gly Ser Thr Ile Gly Cys Gln Arg Leu Ala Gly Arg 865 870 875 880 Leu Ile Pro Arg Ser Tyr Leu Ser Leu Gln Glu Ala Val Leu Ala Glu 885 890 895 Gln Gln Arg Arg Ser Arg Asp Asp Asp Val Gln Tyr Leu Thr Asp Arg 900 905 910 Gln Leu Glu Gln Leu Val Glu Gln Thr Pro Asp Asn Asp Ile Lys Asp 915 920 925 Tyr Glu Asp Leu Gln Ser Ala Ile Ser Phe Leu Ile Glu Thr Gly Thr 930 935 940 Leu Leu His Phe Pro Asp Thr Ser His Gly Leu Arg Asn Leu Tyr Phe 945 950 955 960 Leu Asp Pro Ile Trp Leu Ser Glu Cys Leu Gln Arg Ile Phe Asn Ile 965 970 975 Lys Gly Ser Arg Ser Val Ala Lys Asn Gly Val Ile Arg Ala Glu Asp 980 985 990 Leu Arg Met Leu Leu Val Gly Thr Gly Phe Thr Gln Gln Thr Glu Glu 995 1000 1005 Gln Tyr Phe Gln Phe Leu Ala Lys Phe Glu Ile Ala Leu Pro Val Ala 1010 1015 1020 Asn Asp Ser Tyr Leu Leu Pro His Leu Leu Pro Ser Lys Pro Gly Leu 1025 1030 1035 1040 Asp Thr His Gly Met Arg His Pro Thr Ala Asn Thr Ile Gln Arg Val 1045 1050 1055 Phe Lys Met Ser Phe Val Pro Val Gly Phe Trp Gln Arg Phe Ile Ala 1060 1065 1070 Arg Met Leu Ile Ser Leu Ala Glu Met Asp Leu Gln Leu Phe Glu Asn 1075 1080 1085 Lys Lys Asn Thr Lys Ser Arg Asn Arg Lys Val Thr Ile Tyr Ser Phe 1090 1095 1100 Thr Gly Asn Gln Arg Asn Arg Cys Ser Thr Phe Arg Val Lys Arg Asn 1105 1110 1115 1120 Gln Thr Ile Tyr Trp Gln Glu Gly Leu Leu Val Thr Phe Asp Gly Gly 1125 1130 1135 Tyr Leu Ser Val Glu Ser Ser Asp Val Asn Trp Lys Lys Lys Lys Ser 1140 1145 1150 Gly Gly Met Lys Ile Val Cys Gln Ser Glu Val Arg Asp Phe Ser Ala 1155 1160 1165 Met Ala Phe Ile Thr Asp His Val Asn Ser Leu Ile Asp Gln Trp Phe 1170 1175 1180 Pro Ala Leu Thr Ala Thr Glu Ser Asp Gly Thr Pro Leu Met Glu Gln 1185 1190 1195 1200 Tyr Val Pro Cys Pro Val Cys Glu Thr Ala Trp Ala Gln His Thr Asp 1205 1210 1215 Pro Ser Glu Lys Ser Glu Asp Val Gln Tyr Phe Asp Met Glu Asp Cys 1220 1225 1230 Val Leu Thr Ala Ile Glu Arg Asp Phe Ile Ser Cys Pro Arg His Pro 1235 1240 1245 Asp Leu Pro Val Pro Leu Gln Glu Leu Val Pro Glu Leu Phe Met Thr 1250 1255 1260 Asp Phe Pro Ala Arg Leu Phe Leu Glu Asn Ser Lys Leu Glu His Ser 1265 1270 1275 1280 Glu Asp Glu Gly Ser Val Leu Gly Gln Gly Gly Ser Gly Thr Val Ile 1285 1290 1295 Tyr Arg Ala Arg Tyr Gln Gly Gln Pro Val Ala Val Lys Arg Phe His 1300 1305 1310 Ile Lys Lys Phe Lys Asn Phe Ala Asn Val Pro Ala Asp Thr Met Leu 1315 1320 1325 Arg His Leu Arg Ala Thr Asp Ala Met Lys Asn Phe Ser Glu Phe Arg 1330 1335 1340 Gln Glu Ala Ser Met Leu His Ala Leu Gln His Pro Cys Ile Val Ala 1345 1350 1355 1360 Leu Ile Gly Ile Ser Ile His Pro Leu Cys Phe Ala Leu Glu Leu Ala 1365 1370 1375 Pro Leu Ser Ser Leu Asn Thr Val Leu Ser Glu Asn Ala Arg Asp Ser 1380 1385 1390 Ser Phe Ile Pro Leu Gly His Met Leu Thr Gln Lys Ile Ala Tyr Gln 1395 1400 1405 Ile Ala Ser Gly Leu Ala Tyr Leu His Lys Lys Asn Ile Ile Phe Cys 1410 1415 1420 Asp Leu Lys Ser Asp Asn Ile Leu Val Trp Ser Leu Asp Val Lys Glu 1425 1430 1435 1440 His Ile Asn Ile Lys Leu Ser Asp Tyr Gly Ile Ser Arg Gln Ser Phe 1445 1450 1455 His Glu Gly Ala Leu Gly Val Glu Gly Thr Pro Gly Tyr Gln Ala Pro 1460 1465 1470 Glu Ile Arg Pro Arg Ile Val Tyr Asp Glu Lys Val Asp Met Phe Ser 1475 1480 1485 Tyr Gly Met Val Leu Tyr Glu Leu Leu Ser Gly Gln Arg Pro Ala Leu 1490 1495 1500 Gly His His Gln Leu Gln Ile Ala Lys Lys Leu Ser Lys Gly Ile Arg 1505 1510 1515 1520 Pro Val Leu Gly Gln Pro Glu Glu Val Gln Phe Arg Arg Leu Gln Ala 1525 1530 1535 Leu Met Met Glu Cys Trp Asp Thr Lys Pro Glu Lys Arg Pro Leu Ala 1540 1545 1550 Leu Ser Val Val Ser Gln Met Lys Asp Pro Thr Phe Ala Thr Phe Met 1555 1560 1565 Tyr Glu Leu Cys Cys Gly Lys Gln Thr Ala Phe Phe Ser Ser Gln Gly 1570 1575 1580 Gln Glu Tyr Thr Val Val Phe Trp Asp Gly Lys Glu Glu Ser Arg Asn 1585 1590 1595 1600 Tyr Thr Val Val Asn Thr Glu Lys Gly Leu Met Glu Val Gln Arg Met 1605 1610 1615 Cys Cys Pro Gly Met Lys Val Ser Cys Gln Leu Gln Val Gln Arg Ser 1620 1625 1630 Leu Trp Thr Ala Thr Glu Asn Ser Tyr Leu Val Leu Ala Gly Leu Ala 1635 1640 1645 Asp Gly Leu Val Ala Val Phe Pro Val Val Arg Gly Thr Pro Lys Asp 1650 1655 1660 Ser Cys Ser Tyr Leu Cys Ser His Thr Ala Asn Arg Ser Lys Phe Ser 1665 1670 1675 1680 Ile Ala Asp Glu Asp Ala Arg Gln Asn Pro Tyr Pro Val Lys Ala Met 1685 1690 1695 Glu Val Val Asn Ser Gly Ser Glu Val Trp Tyr Ser Asn Gly Pro Gly 1700 1705 1710 Leu Leu Val Ile Asp Cys Ala Ser Leu Glu Ile Cys Arg Arg Leu Glu 1715 1720 1725 Pro Tyr Met Ala Pro Ser Met Val Thr Ser Val Val Cys Ser Ser Glu 1730 1735 1740 Gly Arg Gly Glu Glu Val Val Trp Cys Leu Asp Asp Lys Ala Asn Ser 1745 1750 1755 1760 Leu Val Met Tyr His Ser Thr Thr Tyr Gln Leu Cys Ala Arg Tyr Phe 1765 1770 1775 Cys Gly Val Pro Ser Pro Leu Arg Asp Met Phe Pro Val Arg Pro Leu 1780 1785 1790 Asp Thr Glu Pro Pro Ala Ala Ser His Thr Ala Asn Pro Lys Val Pro 1795 1800 1805 Glu Gly Asp Ser Ile Ala Asp Val Ser Ile Met Tyr Ser Glu Glu Leu 1810 1815 1820 Gly Thr Gln Ile Leu Ile His Gln Glu Ser Leu Thr Asp Tyr Cys Ser 1825 1830 1835 1840 Met Ser Ser Tyr Ser Ser Ser Pro Pro Arg Gln Ala Ala Arg Ser Pro 1845 1850 1855 Ser Ser Leu Pro Ser Ser Pro Ala Ser Ser Ser Ser Val Pro Phe Ser 1860 1865 1870 Thr Asp Cys Glu Asp Ser Asp Met Leu His Thr Pro Gly Ala Ala Ser 1875 1880 1885 Asp Arg Ser Glu His Asp Leu Thr Pro Met Asp Gly Glu Thr Phe Ser 1890 1895 1900 Gln His Leu Gln Ala Val Lys Ile Leu Ala Val Arg Asp Leu Ile Trp 1905 1910 1915 1920 Val Pro Arg Arg Gly Gly Asp Val Ile Val Ile Gly Leu Glu Lys Asp 1925 1930 1935 Ser Gly Ala Gln Arg Gly Arg Val Ile Ala Val Leu Lys Ala Arg Glu 1940 1945 1950 Leu Thr Pro His Gly Val Leu Val Asp Ala Ala Val Val Ala Lys Asp 1955 1960 1965 Thr Val Val Cys Thr Phe Glu Asn Glu Asn Thr Glu Trp Cys Leu Ala 1970 1975 1980 Val Trp Arg Gly Trp Gly Ala Arg Glu Phe Asp Ile Phe Tyr Gln Ser 1985 1990 1995 2000 Tyr Glu Glu Leu Gly Arg Leu Glu Ala Cys Thr Arg Lys Arg 2005 2010 9 22 DNA Artificial Sequence Description of Artificial Sequence Primer 9 gtatgaactg tgctgtggga ag 22 10 23 DNA Artificial Sequence Description of Artificial Sequence Primer 10 gatgtaccac tccaccacct acc 23 11 20 DNA Artificial Sequence Description of Artificial Sequence Primer 11 atggagacgc ttaacggtgc 20 12 26 DNA Artificial Sequence Description of Artificial Sequence Primer 12 gttccctgtc atcgtgcgct tgcccc 26 13 25 DNA Artificial Sequence Description of Artificial Sequence Primer 13 ccagcaacaa gttgtcccac ctccc 25 14 25 DNA Artificial Sequence Description of Artificial Sequence Primer 14 ggatctctcc agaaaccaac ttggc 25 15 26 DNA Artificial Sequence Description of Artificial Sequence Primer 15 cctggagatc ttacagacgg ggaggg 26 16 25 DNA Artificial Sequence Description of Artificial Sequence Primer 16 cgtcggcagc accatcggct gccag 25 17 24 DNA Artificial Sequence Description of Artificial Sequence Primer 17 cctcctgccc catctccttc catc 24 18 25 DNA Artificial Sequence Description of Artificial Sequence Primer 18 gaaatcagag gatgtgcagt acttc 25 19 24 DNA Artificial Sequence Description of Artificial Sequence Primer 19 caccgtgctg tccgagaacg ccag 24 20 24 DNA Artificial Sequence Description of Artificial Sequence Primer 20 ccttcatgta tgaactgtgc tgtg 24 21 23 DNA Artificial Sequence Description of Artificial Sequence Primer 21 ccatggttac gtcagtcgtg tgc 23 22 23 DNA Artificial Sequence Description of Artificial Sequence Primer 22 ccgacaggtc tgagcatgac ctg 23 23 25 DNA Artificial Sequence Description of Artificial Sequence Primer 23 ttaccttctc ttgcgagtgc aagcc 25 24 21 DNA Artificial Sequence Description of Artificial Sequence Primer 24 gagaactctg ctccagagaa c 21 25 24 DNA Artificial Sequence Description of Artificial Sequence Primer 25 cggatgacaa cccagccgtg gtgg 24 26 10 PRT Artificial Sequence Description of Artificial Sequence Synthetic peptide substrate 26 Lys Lys Leu Asn Arg Thr Leu Ser Val Ala 1 5 10 

1. Nucleic acid that comprises a. The nucleotide sequence that is shown in Seq ID NO 1, Seq ID NO 3, Seq ID NO 5 or Seq ID No 7, b. A nucleotide sequence that corresponds to the sequences of a. within the scope of the degeneration of the genetic code, or c. A nucleotide sequence that hybridizes with the sequences of a. under stringent conditions.
 2. Nucleic acid according to claim 1 that comprises a protein-coding section of the nucleic acid sequence that is shown in Seq ID NO 1, Seq ID NO 3, Seq ID NO 5 or Seq ID No
 7. 3. Nucleic acid that codes for a polypeptide with the amino acid sequence that is shown in Seq ID NO 2, Seq ID NO 4, Seq ID NO 6 or Seq ID NO
 8. 4. Polypeptide that is coded by a nucleic acid according to one of claims 1-3.
 5. Polypeptide that comprises the amino acid sequence that is shown in Seq ID NO 2, Seq ID NO 4, Seq ID NO 6 or Seq ID NO 8 or portions thereof.
 6. Polypeptide that comprises the kinase domain of the amino acid sequence that is shown in Seq ID NO 2, Seq ID NO 4, Seq ID NO 6 or Seq ID NO
 8. 7. Use of a polypeptide according to claim 4, 5 or 6 or of portions of this polypeptide for the production of antibodies.
 8. Antibody against a polypeptide according to one of claims 4 to
 6. 9. Use of a probe with nucleic acid sequences that are complementary to the nucleic acid sequences according to claims 1-3 for the production of a reagent for detecting the presence of mRNA according to one of claims 1 to 3 in cells.
 10. Vector that contains at least one copy of a nucleic acid according to one of claims 1-3.
 11. Cell that is transfixed with a nucleic acid according to one of claims 1-3 or with a vector according to claim
 10. 12. Use of a cell according to claim 11 for the expression of nucleic acid according to one of claims 1-3.
 13. Use of a. A nucleic acid according to one of claims 1 to 3, b. A polypeptide according to one of claims 4 to 6 or c. A cell according to claim 11 for identifying effectors of a polypeptide according to claim 4 or
 5. 14. Use of a nucleic acid according to claims 1 to 3 or a polypeptide according to claims 4 to 6 as a target substance for the production of an agent for steroid hormone-dependent diseases.
 15. Test system for identifying effectors of a polypeptide according to claim 4 or 5, whereby a polypeptide is incubated according to claim 4 or 5 with a steroid, a steroid analog or a sterol, and the amount of bound steroid, steroid analog or sterol is detected.
 16. Test system according to claim 14 or 15 whereby the effectors are FF-MAS agonists or antagonists.
 17. Test system for identifying inhibitors of the kinase function of the polypeptide according to claim 4 or 5, whereby a polypeptide is brought into contact according to claim 4 or 5 with the substances that are to be tested, and the kinase activity is determined.
 18. Process for the preparation of a pharmaceutical agent, whereby a. Substances are brought into contact with a test system according to claim 15, 16 or 17, b. The action of the substances on the test system is measured in comparison to controls, c. A substance that shows a modulation of the activity of the polypeptide according to claim 4 or 5 in step b. is identified, d. And the substance that is identified in step c. is mixed with the formulation substances that are commonly used in pharmaceutics. 